RIP at the Synapse and the Role of Intracellular Domains in Neurons

Lee, Yan Jun; Ch’ng, Toh Hean

doi:10.1007/s12017-019-08556-4

RIP at the Synapse and the Role of Intracellular Domains in Neurons

Review Paper
Published: 25 July 2019

Volume 22, pages 1–24, (2020)
Cite this article

NeuroMolecular Medicine Aims and scope Submit manuscript

1140 Accesses
4 Citations
Explore all metrics

Abstract

Regulated intramembrane proteolysis (RIP) occurs in a cell when transmembrane proteins are cleaved by intramembrane proteases such as secretases to generate soluble protein fragments in the extracellular environment and the cytosol. In the cytosol, these soluble intracellular domains (ICDs) have local functions near the site of cleavage or in many cases, translocate to the nucleus to modulate gene expression. While the mechanism of RIP is relatively well studied, the fate and function of ICDs for most substrate proteins remain poorly characterized. In neurons, RIP occurs in various subcellular compartments including at the synapse. In this review, we summarize current research on RIP in neurons, focusing specifically on synaptic proteins where the presence and function of the ICDs have been reported. We also briefly discuss activity-driven processing of RIP substrates at the synapse and the cellular machinery that support long-distance transport of ICDs from the synapse to the nucleus. Finally, we describe future challenges in this field of research in the context of understanding the contribution of ICDs in neuronal function.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Autophagy and the endolysosomal system in presynaptic function

Article Open access 19 December 2020

Maria Andres-Alonso, Michael R. Kreutz & Anna Karpova

The Role of Tomosyn in the Regulation of Neurotransmitter Release

The synaptic proteome

Article 20 July 2014

Melanie Laßek, Jens Weingarten & Walter Volknandt

References

Abbott, M. A., Wells, D. G., & Fallon, J. R. (1999). The insulin receptor tyrosine kinase substrate p58/53 and the insulin receptor are components of CNS synapses. Journal of Neuroscience,19(17), 7300–7308.
Article CAS Google Scholar
Ables, J. L., Breunig, J. J., Eisch, A. J., & Rakic, P. (2011). Not(ch) just development: Notch signalling in the adult brain. Nature Reviews Neuroscience,12(5), 269–283. https://doi.org/10.1038/nrn3024.
Article CAS PubMed PubMed Central Google Scholar
Acx, H., Serneels, L., Radaelli, E., Muyldermans, S., Vincke, C., Pepermans, E., et al. (2017). Inactivation of gamma-secretases leads to accumulation of substrates and non-Alzheimer neurodegeneration. EMBO Molecular Medicine,9(8), 1088–1099. https://doi.org/10.15252/emmm.201707561.
Article CAS PubMed PubMed Central Google Scholar
Akin, O., & Zipursky, S. L. (2016). Frazzled promotes growth cone attachment at the source of a Netrin gradient in the Drosophila visual system. Elife,5, e20762. https://doi.org/10.7554/elife.20762.
Article CAS PubMed PubMed Central Google Scholar
Alberi, L., Liu, S., Wang, Y., Badie, R., Smith-Hicks, C., Wu, J., et al. (2011). Activity-induced Notch signaling in neurons requires Arc/Arg3.1 and is essential for synaptic plasticity in hippocampal networks. Neuron,69(3), 437–444. https://doi.org/10.1016/j.neuron.2011.01.004.
Article CAS PubMed PubMed Central Google Scholar
Allison, J. G., Das, P. M., Ma, J., Inglis, F. M., & Jones, F. E. (2011). The ERBB4 intracellular domain (4ICD) regulates NRG1-induced gene expression in hippocampal neurons. Neuroscience Research,70(2), 155–163. https://doi.org/10.1016/j.neures.2011.02.009.
Article CAS PubMed Google Scholar
Anders, L., Mertins, P., Lammich, S., Murgia, M., Hartmann, D., Saftig, P., et al. (2006). Furin-, ADAM 10-, and gamma-secretase-mediated cleavage of a receptor tyrosine phosphatase and regulation of beta-catenin’s transcriptional activity. Molecular and Cellular Biology,26(10), 3917–3934. https://doi.org/10.1128/mcb.26.10.3917-3934.2006.
Article CAS PubMed PubMed Central Google Scholar
Auffret, A., Gautheron, V., Mattson, M. P., Mariani, J., & Rovira, C. (2010). Progressive age-related impairment of the late long-term potentiation in Alzheimer’s disease presenilin-1 mutant knock-in mice. Journal of Alzheimers Disease,19(3), 1021–1033. https://doi.org/10.3233/jad-2010-1302.
Article CAS Google Scholar
Azuara-Medina, P. M., Sandoval-Duarte, A. M., Morales-Lazaro, S. L., Modragon-Gonzalez, R., Velez-Aguilera, G., Gomez-Lopez, J. D., et al. (2019). The intracellular domain of beta-dystroglycan mediates the nucleolar stress response by suppressing UBF transcriptional activity. Cell Death and Disease,10(3), 196. https://doi.org/10.1038/s41419-019-1454-z.
Article PubMed Google Scholar
Baleriola, J., Walker, C. A., Jean, Y. Y., Crary, J. F., Troy, C. M., Nagy, P. L., et al. (2014). Axonally synthesized ATF4 transmits a neurodegenerative signal across brain regions. Cell,158(5), 1159–1172. https://doi.org/10.1016/j.cell.2014.07.001.
Article CAS PubMed PubMed Central Google Scholar
Balmaceda, V., Cuchillo-Ibanez, I., Pujadas, L., Garcia-Ayllon, M. S., Saura, C. A., Nimpf, J., et al. (2014). ApoER2 processing by presenilin-1 modulates reelin expression. The FASEB Journal,28(4), 1543–1554. https://doi.org/10.1096/fj.13-239350.
Article CAS PubMed Google Scholar
Bao, J., Lin, H., Ouyang, Y., Lei, D., Osman, A., Kim, T. W., et al. (2004). Activity-dependent transcription regulation of PSD-95 by neuregulin-1 and Eos. Nature Neuroscience,7(11), 1250–1258. https://doi.org/10.1038/nn1342.
Article CAS PubMed Google Scholar
Bao, J., Wolpowitz, D., Role, L. W., & Talmage, D. A. (2003). Back signaling by the Nrg-1 intracellular domain. Journal of Cell Biology,161(6), 1133–1141. https://doi.org/10.1083/jcb.200212085.
Article CAS PubMed Google Scholar
Barthet, G., Jorda-Siquier, T., Rumi-Masante, J., Bernadou, F., Muller, U., & Mulle, C. (2018). Presenilin-mediated cleavage of APP regulates synaptotagmin-7 and presynaptic plasticity. Nature Communications,9(1), 4780. https://doi.org/10.1038/s41467-018-06813-x.
Article CAS PubMed PubMed Central Google Scholar
Beffert, U., Weeber, E. J., Durudas, A., Qiu, S., Masiulis, I., Sweatt, J. D., et al. (2005). Modulation of synaptic plasticity and memory by Reelin involves differential splicing of the lipoprotein receptor Apoer2. Neuron,47(4), 567–579. https://doi.org/10.1016/j.neuron.2005.07.007.
Article CAS PubMed Google Scholar
Bhat, P., Chakrabarty, M., Thawani, V., & Saxena, A. (2012). Signalled roads to memory and its degeneration. Annals of Neuroscience,19(2), 84–87. https://doi.org/10.5214/ans.0972.7531.12190209.
Article CAS Google Scholar
Bloch, L., Sineshchekova, O., Reichenbach, D., Reiss, K., Saftig, P., Kuro-o, M., et al. (2009). Klotho is a substrate for alpha-, beta- and gamma-secretase. FEBS Letters,583(19), 3221–3224. https://doi.org/10.1016/j.febslet.2009.09.009.
Article CAS PubMed PubMed Central Google Scholar
Bohm, C., Seibel, N. M., Henkel, B., Steiner, H., Haass, C., & Hampe, W. (2006). SorLA signaling by regulated intramembrane proteolysis. Journal of Biological Chemistry,281(21), 14547–14553. https://doi.org/10.1074/jbc.M601660200.
Article CAS PubMed Google Scholar
Bonn, S., Seeburg, P. H., & Schwarz, M. K. (2007). Combinatorial expression of alpha- and gamma-protocadherins alters their presenilin-dependent processing. Molecular and Cellular Biology,27(11), 4121–4132. https://doi.org/10.1128/mcb.01708-06.
Article CAS PubMed PubMed Central Google Scholar
Borcel, E., Palczynska, M., Krzisch, M., Dimitrov, M., Ulrich, G., Toni, N., et al. (2016). Shedding of neurexin 3beta ectodomain by ADAM10 releases a soluble fragment that affects the development of newborn neurons. Science Reports,6, 39310. https://doi.org/10.1038/srep39310.
Article CAS Google Scholar
Bot, N., Schweizer, C., Ben Halima, S., & Fraering, P. C. (2011). Processing of the synaptic cell adhesion molecule neurexin-3beta by Alzheimer disease alpha- and gamma-secretases. Journal of Biological Chemistry,286(4), 2762–2773. https://doi.org/10.1074/jbc.M110.142521.
Article CAS PubMed Google Scholar
Branca, C., Sarnico, I., Ruotolo, R., Lanzillotta, A., Viscomi, A. R., Benarese, M., et al. (2014). Pharmacological targeting of the beta-amyloid precursor protein intracellular domain. Science Reports,4, 4618. https://doi.org/10.1038/srep04618.
Article CAS Google Scholar
Bray, S. J. (2016). Notch signalling in context. Nature Reviews Molecular Cell Biology,17(11), 722–735. https://doi.org/10.1038/nrm.2016.94.
Article CAS PubMed Google Scholar
Breiderhoff, T., Christiansen, G. B., Pallesen, L. T., Vaegter, C., Nykjaer, A., Holm, M. M., et al. (2013). Sortilin-related receptor SORCS3 is a postsynaptic modulator of synaptic depression and fear extinction. PLoS ONE,8(9), e75006. https://doi.org/10.1371/journal.pone.0075006.
Article CAS PubMed PubMed Central Google Scholar
Brown, M. S., Ye, J., Rawson, R. B., & Goldstein, J. L. (2000). Regulated intramembrane proteolysis: A control mechanism conserved from bacteria to humans. Cell,100(4), 391–398.
Article CAS Google Scholar
Buonanno, A. (2010). The neuregulin signaling pathway and schizophrenia: From genes to synapses and neural circuits. Brain Research Bulletin,83(3–4), 122–131. https://doi.org/10.1016/j.brainresbull.2010.07.012.
Article CAS PubMed PubMed Central Google Scholar
Burden-Gulley, S. M., & Brady-Kalnay, S. M. (1999). PTPmu regulates N-cadherin-dependent neurite outgrowth. Journal of Cell Biology,144(6), 1323–1336. https://doi.org/10.1083/jcb.144.6.1323.
Article CAS PubMed Google Scholar
Burgoyne, A. M., Phillips-Mason, P. J., Burden-Gulley, S. M., Robinson, S., Sloan, A. E., Miller, R. H., et al. (2009). Proteolytic cleavage of protein tyrosine phosphatase mu regulates glioblastoma cell migration. Cancer Research,69(17), 6960–6968. https://doi.org/10.1158/0008-5472.can-09-0863.
Article CAS PubMed PubMed Central Google Scholar
Cai, J., Wu, L., Qi, X., Li Calzi, S., Caballero, S., Shaw, L., et al. (2011). PEDF regulates vascular permeability by a gamma-secretase-mediated pathway. PLoS ONE,6(6), e21164. https://doi.org/10.1371/journal.pone.0021164.
Article CAS PubMed PubMed Central Google Scholar
Cao, X., & Sudhof, T. C. (2001). A transcriptionally [correction of transcriptively] active complex of APP with Fe65 and histone acetyltransferase Tip60. Science,293(5527), 115–120. https://doi.org/10.1126/science.1058783.
Article CAS PubMed Google Scholar
Cao, X., & Sudhof, T. C. (2004). Dissection of amyloid-beta precursor protein-dependent transcriptional transactivation. Journal of Biological Chemistry,279(23), 24601–24611. https://doi.org/10.1074/jbc.M402248200.
Article CAS PubMed Google Scholar
Cau, E., & Blader, P. (2009). Notch activity in the nervous system: To switch or not switch? Neural Development,4, 36. https://doi.org/10.1186/1749-8104-4-36.
Article CAS PubMed PubMed Central Google Scholar
Ch’ng, T. H., Uzgil, B., Lin, P., Avliyakulov, N. K., O’Dell, T. J., & Martin, K. C. (2012). Activity-dependent transport of the transcriptional coactivator CRTC1 from synapse to nucleus. Cell,150(1), 207–221. https://doi.org/10.1016/j.cell.2012.05.027.
Article CAS PubMed PubMed Central Google Scholar
Chang, K. A., & Suh, Y. H. (2010). Possible roles of amyloid intracellular domain of amyloid precursor protein. BMB Reports,43(10), 656–663. https://doi.org/10.5483/BMBRep.2010.43.10.656.
Article CAS PubMed Google Scholar
Chao, M. V., & Hempstead, B. L. (1995). p75 and Trk: A two-receptor system. Trends in Neurosciences,18(7), 321–326.
Article CAS Google Scholar
Chen, Y., Hancock, M. L., Role, L. W., & Talmage, D. A. (2010). Intramembranous valine linked to schizophrenia is required for neuregulin 1 regulation of the morphological development of cortical neurons. Journal of Neuroscience,30(27), 9199–9208. https://doi.org/10.1523/jneurosci.0605-10.2010.
Article CAS PubMed Google Scholar
Chen, A. C., & Selkoe, D. J. (2007). Presenilin-dependent transcriptional control of the abeta-degrading enzyme neprilysin by intracellular domains of betaAPP and APLP. Neuron,46, 541–554. https://doi.org/10.1016/j.neuron.2007.01.023.
Article CAS Google Scholar
Cheng, P., & Gabrilovich, D. (2008). Notch signaling in differentiation and function of dendritic cells. Immunologic Research,41(1), 1–14. https://doi.org/10.1007/s12026-007-8011-z.
Article CAS PubMed PubMed Central Google Scholar
Cheung, K. H., Mei, L., Mak, D. O., Hayashi, I., Iwatsubo, T., Kang, D. E., et al. (2010). Gain-of-function enhancement of IP3 receptor modal gating by familial Alzheimer’s disease-linked presenilin mutants in human cells and mouse neurons. Science Signal,3(114), ra22. https://doi.org/10.1126/scisignal.2000818.
Article CAS Google Scholar
Chook, Y. M., & Suel, K. E. (2011). Nuclear import by karyopherin-betas: Recognition and inhibition. Biochimica et Biophysica Acta,1813(9), 1593–1606. https://doi.org/10.1016/j.bbamcr.2010.10.014.
Article CAS PubMed Google Scholar
Chow, J. P., Fujikawa, A., Shimizu, H., & Noda, M. (2008a). Plasmin-mediated processing of protein tyrosine phosphatase receptor type Z in the mouse brain. Neuroscience Letters,442(3), 208–212. https://doi.org/10.1016/j.neulet.2008.07.028.
Article CAS PubMed Google Scholar
Chow, J. P., Fujikawa, A., Shimizu, H., Suzuki, R., & Noda, M. (2008b). Metalloproteinase- and gamma-secretase-mediated cleavage of protein-tyrosine phosphatase receptor type Z. Journal of Biological Chemistry,283(45), 30879–30889. https://doi.org/10.1074/jbc.M802976200.
Article CAS PubMed Google Scholar
Christiansen, G. B., Andersen, K. H., Riis, S., Nykjaer, A., Bolcho, U., Jensen, M. S., et al. (2017). The sorting receptor SorCS3 is a stronger regulator of glutamate receptor functions compared to GABAergic mechanisms in the hippocampus. Hippocampus,27(3), 235–248. https://doi.org/10.1002/hipo.22689.
Article CAS PubMed Google Scholar
Conrad, S., Genth, H., Hofmann, F., Just, I., & Skutella, T. (2007). Neogenin-RGMa signaling at the growth cone is bone morphogenetic protein-independent and involves RhoA, ROCK, and PKC. Journal of Biological Chemistry,282(22), 16423–16433. https://doi.org/10.1074/jbc.M610901200.
Article CAS PubMed Google Scholar
Cox, L. J., Hengst, U., Gurskaya, N. G., Lukyanov, K. A., & Jaffrey, S. R. (2008). Intra-axonal translation and retrograde trafficking of CREB promotes neuronal survival. Nature Cell Biology,10(2), 149–159. https://doi.org/10.1038/ncb1677.
Article CAS PubMed PubMed Central Google Scholar
Cupers, P., Orlans, I., Craessaerts, K., Annaert, W., & De Strooper, B. (2001). The amyloid precursor protein (APP)-cytoplasmic fragment generated by gamma-secretase is rapidly degraded but distributes partially in a nuclear fraction of neurones in culture. Journal of Neurochemistry,78(5), 1168–1178.
Article CAS Google Scholar
De Falco, V., Tamburrino, A., Ventre, S., Castellone, M. D., Malek, M., Manie, S. N., et al. (2012). CD44 proteolysis increases CREB phosphorylation and sustains proliferation of thyroid cancer cells. Cancer Research,72(6), 1449–1458. https://doi.org/10.1158/0008-5472.can-11-3320.
Article PubMed Google Scholar
De Felice, F. G., Vieira, M. N., Bomfim, T. R., Decker, H., Velasco, P. T., Lambert, M. P., et al. (2009). Protection of synapses against Alzheimer’s-linked toxins: Insulin signaling prevents the pathogenic binding of Abeta oligomers. Proceedings of National Academy of Science USA,106(6), 1971–1976. https://doi.org/10.1073/pnas.0809158106.
Article Google Scholar
De Rossi, P., Harde, E., Dupuis, J. P., Martin, L., Chounlamountri, N., Bardin, M., et al. (2016). A critical role for VEGF and VEGFR2 in NMDA receptor synaptic function and fear-related behavior. Molecular Psychiatry,21(12), 1768–1780. https://doi.org/10.1038/mp.2015.195.
Article CAS PubMed PubMed Central Google Scholar
Deregowski, V., Gazzerro, E., Priest, L., Rydziel, S., & Canalis, E. (2006). Role of the RAM domain and ankyrin repeats on notch signaling and activity in cells of osteoblastic lineage. Journal of Bone and Mineral Research,21(8), 1317–1326. https://doi.org/10.1359/jbmr.060505.
Article CAS PubMed Google Scholar
Dias, B. G., Goodman, J. V., Ahluwalia, R., Easton, A. E., Andero, R., & Ressler, K. J. (2014). Amygdala-dependent fear memory consolidation via miR-34a and Notch signaling. Neuron,83(4), 906–918. https://doi.org/10.1016/j.neuron.2014.07.019.
Article CAS PubMed PubMed Central Google Scholar
DiBattista, A. M., Dumanis, S. B., Song, J. M., Bu, G., Weeber, E., Rebeck, G. W., et al. (2015). Very low density lipoprotein receptor regulates dendritic spine formation in a RasGRF1/CaMKII dependent manner. Biochimica et Biophysica Acta,1853(5), 904–917. https://doi.org/10.1016/j.bbamcr.2015.01.015.
Article CAS PubMed PubMed Central Google Scholar
Dieterich, D. C., Karpova, A., Mikhaylova, M., Zdobnova, I., Konig, I., Landwehr, M., et al. (2008). Caldendrin-Jacob: A protein liaison that couples NMDA receptor signalling to the nucleus. PLoS Biology,6(2), e34. https://doi.org/10.1371/journal.pbio.0060034.
Article CAS PubMed PubMed Central Google Scholar
Ding, X. F., Gao, X., Ding, X. C., Fan, M., & Chen, J. (2016). Postnatal dysregulation of Notch signal disrupts dendrite development of adult-born neurons in the hippocampus and contributes to memory impairment. Science Reports,6, 25780. https://doi.org/10.1038/srep25780.
Article CAS Google Scholar
Dlugosz, P., & Nimpf, J. (2018). The reelin receptors apolipoprotein E receptor 2 (ApoER2) and VLDL receptor. International Journal of Molecular Sciences,19(10), 3090. https://doi.org/10.3390/ijms19103090.
Article CAS PubMed Central Google Scholar
Dobrowsky, R. T., Werner, M. H., Castellino, A. M., Chao, M. V., & Hannun, Y. A. (1994). Activation of the sphingomyelin cycle through the low-affinity neurotrophin receptor. Science,265(5178), 1596–1599.
Article CAS Google Scholar
Drosopoulos, N. E., Walsh, F. S., & Doherty, P. (1999). A soluble version of the receptor-like protein tyrosine phosphatase kappa stimulates neurite outgrowth via a Grb2/MEK1-dependent signaling cascade. Molecular and Cellular Neuroscience,13(6), 441–449. https://doi.org/10.1006/mcne.1999.0758.
Article CAS PubMed Google Scholar
Dumanis, S. B., Chamberlain, K. A., Jin Sohn, Y., Jin Lee, Y., Guenette, S. Y., Suzuki, T., et al. (2012). FE65 as a link between VLDLR and APP to regulate their trafficking and processing. Molecular Neurodegener,7, 9. https://doi.org/10.1186/1750-1326-7-9.
Article CAS Google Scholar
Eggert, S., Paliga, K., Soba, P., Evin, G., Masters, C. L., Weidemann, A., et al. (2004). The proteolytic processing of the amyloid precursor protein gene family members APLP-1 and APLP-2 involves alpha-, beta-, gamma-, and epsilon-like cleavages: Modulation of APLP-1 processing by n-glycosylation. Journal of Biological Chemistry,279(18), 18146–18156. https://doi.org/10.1074/jbc.M311601200.
Article CAS PubMed Google Scholar
Fazzari, P., Snellinx, A., Sabanov, V., Ahmed, T., Serneels, L., Gartner, A., et al. (2014). Cell autonomous regulation of hippocampal circuitry via Aph1b-gamma-secretase/neuregulin 1 signalling. Elife,3, 02196. https://doi.org/10.7554/elife.02196.
Article Google Scholar
Fleck, D., Voss, M., Brankatschk, B., Giudici, C., Hampel, H., Schwenk, B., et al. (2016). Proteolytic processing of neuregulin 1 type III by three intramembrane-cleaving proteases. Journal of Biological Chemistry,291(1), 318–333. https://doi.org/10.1074/jbc.M115.697995.
Article CAS PubMed Google Scholar
Fogel, A. I., Akins, M. R., Krupp, A. J., Stagi, M., Stein, V., & Biederer, T. (2007). SynCAMs organize synapses through heterophilic adhesion. Journal of Neuroscience,27(46), 12516–12530. https://doi.org/10.1523/jneurosci.2739-07.2007.
Article CAS PubMed Google Scholar
Forwood, J. K., Harley, V., & Jans, D. A. (2001). The C-terminal nuclear localization signal of the sex-determining region Y (SRY) high mobility group domain mediates nuclear import through importin beta 1. Journal of Biological Chemistry,276(49), 46575–46582. https://doi.org/10.1074/jbc.M101668200.
Article CAS PubMed Google Scholar
Frykman, S., Hur, J. Y., Franberg, J., Aoki, M., Winblad, B., Nahalkova, J., et al. (2010). Synaptic and endosomal localization of active gamma-secretase in rat brain. PLoS ONE,5(1), e8948. https://doi.org/10.1371/journal.pone.0008948.
Article CAS PubMed PubMed Central Google Scholar
Galeano, P., Leal, M. C., Ferrari, C. C., Dalmasso, M. C., Martino Adami, P. V., Farias, M. I., et al. (2018). Chronic hippocampal expression of notch intracellular domain induces vascular thickening, reduces glucose availability, and exacerbates spatial memory deficits in a rat model of early alzheimer. Molecular Neurobiology,55(11), 8637–8650. https://doi.org/10.1007/s12035-018-1002-3.
Article CAS PubMed Google Scholar
Gan, M., Jiang, P., McLean, P., Kanekiyo, T., & Bu, G. (2014). Low-density lipoprotein receptor-related protein 1 (LRP1) regulates the stability and function of GluA1 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor in neurons. PLoS ONE,9(12), e113237. https://doi.org/10.1371/journal.pone.0113237.
Article CAS PubMed PubMed Central Google Scholar
Ganguly, A., DeMott, L., Zhu, C., McClosky, D. D., Anderson, C. T., & Dixit, R. (2018). Importin-beta directly regulates the motor activity and turnover of a kinesin-4. Developmental Cell,44(5), 642–651.e645. https://doi.org/10.1016/j.devcel.2018.01.027.
Article CAS PubMed Google Scholar
Gatto, G., Morales, D., Kania, A., & Klein, R. (2014). EphA4 receptor shedding regulates spinal motor axon guidance. Current Biology,24(20), 2355–2365. https://doi.org/10.1016/j.cub.2014.08.028.
Article CAS PubMed Google Scholar
Gazit, N., Vertkin, I., Shapira, I., Helm, M., Slomowitz, E., Sheiba, M., et al. (2016). IGF-1 receptor differentially regulates spontaneous and evoked transmission via mitochondria at hippocampal synapses. Neuron,89(3), 583–597. https://doi.org/10.1016/j.neuron.2015.12.034.
Article CAS PubMed PubMed Central Google Scholar
Georgakopoulos, A., Litterst, C., Ghersi, E., Baki, L., Xu, C., Serban, G., et al. (2006). Metalloproteinase/Presenilin1 processing of ephrinB regulates EphB-induced Src phosphorylation and signaling. EMBO Journal,25(6), 1242–1252. https://doi.org/10.1038/sj.emboj.7601031.
Article CAS PubMed Google Scholar
Gersbacher, M. T., Goodger, Z. V., Trutzel, A., Bundschuh, D., Nitsch, R. M., & Konietzko, U. (2013). Turnover of amyloid precursor protein family members determines their nuclear signaling capability. PLoS ONE,8(7), e69363. https://doi.org/10.1371/journal.pone.0069363.
Article CAS PubMed PubMed Central Google Scholar
Goldschneider, D., Rama, N., Guix, C., & Mehlen, P. (2008). The neogenin intracellular domain regulates gene transcription via nuclear translocation. Molecular and Cellular Biology,28(12), 4068–4079. https://doi.org/10.1128/mcb.02114-07.
Article CAS PubMed PubMed Central Google Scholar
Gordon, W. R., Roy, M., Vardar-Ulu, D., Garfinkel, M., Mansour, M. R., Aster, J. C., et al. (2009). Structure of the Notch1-negative regulatory region: Implications for normal activation and pathogenic signaling in T-ALL. Blood,113(18), 4381–4390. https://doi.org/10.1182/blood-2008-08-174748.
Article CAS PubMed PubMed Central Google Scholar
Grimm, M. O., Mett, J., Stahlmann, C. P., Grosgen, S., Haupenthal, V. J., Blumel, T., et al. (2015). APP intracellular domain derived from amyloidogenic beta- and gamma-secretase cleavage regulates neprilysin expression. Frontiers in Aging Neuroscience,7, 77. https://doi.org/10.3389/fnagi.2015.00077.
Article CAS PubMed PubMed Central Google Scholar
Guo, Q., Li, H., Gaddam, S. S., Justice, N. J., Robertson, C. S., & Zheng, H. (2012). Amyloid precursor protein revisited: Neuron-specific expression and highly stable nature of soluble derivatives. Journal of Biological Chemistry,287(4), 2437–2445. https://doi.org/10.1074/jbc.M111.315051.
Article CAS PubMed Google Scholar
Haapasalo, A., Kim, D. Y., Carey, B. W., Turunen, M. K., Pettingell, W. H., & Kovacs, D. M. (2007). Presenilin/gamma-secretase-mediated cleavage regulates association of leukocyte-common antigen-related (LAR) receptor tyrosine phosphatase with beta-catenin. Journal of Biological Chemistry,282(12), 9063–9072. https://doi.org/10.1074/jbc.M611324200.
Article CAS PubMed Google Scholar
Haapasalo, A., & Kovacs, D. M. (2011). The many substrates of presenilin/gamma-secretase. Journal of Alzheimer’s Disease,25(1), 3–28. https://doi.org/10.3233/jad-2011-101065.
Article CAS PubMed PubMed Central Google Scholar
Haas, I. G., Frank, M., Veron, N., & Kemler, R. (2005). Presenilin-dependent processing and nuclear function of gamma-protocadherins. Journal of Biological Chemistry,280(10), 9313–9319. https://doi.org/10.1074/jbc.M412909200.
Article CAS PubMed Google Scholar
Hallaq, R., Volpicelli, F., Cuchillo-Ibanez, I., Hooper, C., Mizuno, K., Uwanogho, D., et al. (2015). The Notch intracellular domain represses CRE-dependent transcription. Cellular Signalling,27(3), 621–629. https://doi.org/10.1016/j.cellsig.2014.11.034.
Article CAS PubMed Google Scholar
Hambsch, B., Grinevich, V., Seeburg, P. H., & Schwarz, M. K. (2005). {gamma}-Protocadherins, presenilin-mediated release of C-terminal fragment promotes locus expression. Journal of Biological Chemistry,280(16), 15888–15897. https://doi.org/10.1074/jbc.M414359200.
Article CAS PubMed Google Scholar
Hartl, D., Nebrich, G., Klein, O., Stephanowitz, H., Krause, E., & Rohe, M. (2016). SORLA regulates calpain-dependent degradation of synapsin. Alzheimers and Dementia,12(9), 952–963. https://doi.org/10.1016/j.jalz.2016.02.008.
Article Google Scholar
Hatzimanolis, A., McGrath, J. A., Wang, R., Li, T., Wong, P. C., Nestadt, G., et al. (2013). Multiple variants aggregate in the neuregulin signaling pathway in a subset of schizophrenia patients. Translational Psychiatry,3, e264. https://doi.org/10.1038/tp.2013.33.
Article CAS PubMed PubMed Central Google Scholar
Hayashi, N., Oohira, A., & Miyata, S. (2005). Synaptic localization of receptor-type protein tyrosine phosphatase zeta/beta in the cerebral and hippocampal neurons of adult rats. Brain Research,1050(1–2), 163–169. https://doi.org/10.1016/j.brainres.2005.05.047.
Article CAS PubMed Google Scholar
Hayashida, K., Bartlett, A. H., Chen, Y., & Park, P. W. (2010). Molecular and cellular mechanisms of ectodomain shedding. The Anatomical Record (Hoboken),293(6), 925–937. https://doi.org/10.1002/ar.20757.
Article CAS Google Scholar
Heber, S., Herms, J., Gajic, V., Hainfellner, J., Aguzzi, A., Rulicke, T., et al. (2000). Mice with combined gene knock-outs reveal essential and partially redundant functions of amyloid precursor protein family members. Journal of Neuroscience,20(21), 7951–7963.
Article CAS Google Scholar
Hebert, S. S., Serneels, L., Tolia, A., Craessaerts, K., Derks, C., Filippov, M. A., et al. (2006). Regulated intramembrane proteolysis of amyloid precursor protein and regulation of expression of putative target genes. EMBO Reports,7(7), 739–745. https://doi.org/10.1038/sj.embor.7400704.
Article CAS PubMed PubMed Central Google Scholar
Heitzler, P. (2010). Biodiversity and noncanonical Notch signaling. Current Topics in Developmental Biology,92, 457–481. https://doi.org/10.1016/s0070-2153(10)92014-0.
Article CAS PubMed Google Scholar
Henriques, A. G., Vieira, S. I., da Cruz e Silva, E. F., & da Cruz e Silva, O. A. (2009). Alphabeta hinders nuclear targeting of AICD and Fe65 in primary neuronal cultures. Journal of Molecular Neuroscience,39(1–2), 248–255. https://doi.org/10.1007/s12031-009-9192-9.
Article CAS PubMed PubMed Central Google Scholar
Herbst, W. A., & Martin, K. C. (2017). Regulated transport of signaling proteins from synapse to nucleus. Current Opinion in Neurobiology,45, 78–84. https://doi.org/10.1016/j.conb.2017.04.006.
Article CAS PubMed PubMed Central Google Scholar
Hiramoto, M., Hiromi, Y., Giniger, E., & Hotta, Y. (2000). The Drosophila Netrin receptor Frazzled guides axons by controlling Netrin distribution. Nature,406(6798), 886–889. https://doi.org/10.1038/35022571.
Article CAS PubMed Google Scholar
Ho, A., & Shen, J. (2011). Presenilins in synaptic function and disease. Trends in Molecular Medicine,17(11), 617–624. https://doi.org/10.1016/j.molmed.2011.06.002.
Article CAS PubMed PubMed Central Google Scholar
Hoe, H. S., & Rebeck, G. W. (2005). Regulation of ApoE receptor proteolysis by ligand binding. Brain Research,137(1–2), 31–39. https://doi.org/10.1016/j.molbrainres.2005.02.013.
Article CAS PubMed Google Scholar
Honda, T., & Nakajima, K. (2016). Proper level of cytosolic disabled-1, which is regulated by dual nuclear translocation pathways, is important for cortical neuronal migration. Cerebral Cortex,26(7), 3219–3236. https://doi.org/10.1093/cercor/bhv162.
Article PubMed Google Scholar
Horn, K. E., Glasgow, S. D., Gobert, D., Bull, S. J., Luk, T., Girgis, J., et al. (2013). DCC expression by neurons regulates synaptic plasticity in the adult brain. Cell Reports,3(1), 173–185. https://doi.org/10.1016/j.celrep.2012.12.005.
Article CAS PubMed Google Scholar
Hsueh, Y. P., Roberts, A. M., Volta, M., Sheng, M., & Roberts, R. G. (2001). Bipartite interaction between neurofibromatosis type I protein (neurofibromin) and syndecan transmembrane heparan sulfate proteoglycans. Journal of Neuroscience,21(11), 3764–3770.
Article CAS Google Scholar
Huang, T. Y., Zhao, Y., Jiang, L. L., Li, X., Liu, Y., Sun, Y., et al. (2017). SORLA attenuates EphA4 signaling and amyloid beta-induced neurodegeneration. Journal of Experimental Medicine,214(12), 3669–3685. https://doi.org/10.1084/jem.20171413.
Article CAS PubMed Google Scholar
Huenniger, K., Kramer, A., Soom, M., Chang, I., Kohler, M., Depping, R., et al. (2010). Notch1 signaling is mediated by importins alpha 3, 4, and 7. Cellular and Molecular Life Sciences,67(18), 3187–3196. https://doi.org/10.1007/s00018-010-0378-7.
Article CAS PubMed PubMed Central Google Scholar
Imamoto, N., & Kose, S. (2012). Heat-shock stress activates a novel nuclear import pathway mediated by Hikeshi. Nucleus,3(5), 422–428. https://doi.org/10.4161/nucl.21713.
Article PubMed PubMed Central Google Scholar
Inoue, E., Deguchi-Tawarada, M., Togawa, A., Matsui, C., Arita, K., Katahira-Tayama, S., et al. (2009). Synaptic activity prompts gamma-secretase-mediated cleavage of EphA4 and dendritic spine formation. Journal of Cell Biology,185(3), 551–564. https://doi.org/10.1083/jcb.200809151.
Article CAS PubMed Google Scholar
Ivanova, D., Dirks, A., Montenegro-Venegas, C., Schone, C., Altrock, W. D., Marini, C., et al. (2015). Synaptic activity controls localization and function of CtBP1 via binding to Bassoon and Piccolo. EMBO Journal,34(8), 1056–1077. https://doi.org/10.15252/embj.201488796.
Article CAS PubMed Google Scholar
Iwakura, Y., & Nawa, H. (2013). ErbB1-4-dependent EGF/neuregulin signals and their cross talk in the central nervous system: Pathological implications in schizophrenia and Parkinson’s disease. Frontiers in Cellular Neuroscience,7, 4. https://doi.org/10.3389/fncel.2013.00004.
Article PubMed PubMed Central Google Scholar
Jeffrey, R. A., Ch’ng, T. H., O’Dell, T. J., & Martin, K. C. (2009). Activity-dependent anchoring of importin alpha at the synapse involves regulated binding to the cytoplasmic tail of the NR1-1a subunit of the NMDA receptor. Journal of Neuroscience,29(50), 15613–15620. https://doi.org/10.1523/jneurosci.3314-09.2009.
Article CAS PubMed Google Scholar
Jordan, B. A., & Kreutz, M. R. (2009). Nucleocytoplasmic protein shuttling: The direct route in synapse-to-nucleus signaling. Trends in Neurosciences,32(7), 392–401. https://doi.org/10.1016/j.tins.2009.04.001.
Article CAS PubMed Google Scholar
Jung, K. M., Tan, S., Landman, N., Petrova, K., Murray, S., Lewis, R., et al. (2003). Regulated intramembrane proteolysis of the p75 neurotrophin receptor modulates its association with the TrkA receptor. Journal of Biological Chemistry,278(43), 42161–42169. https://doi.org/10.1074/jbc.M306028200.
Article CAS PubMed Google Scholar
Kamenetz, F., Tomita, T., Hsieh, H., Seabrook, G., Borchelt, D., Iwatsubo, T., et al. (2003). APP processing and synaptic function. Neuron,37(6), 925–937.
Article CAS Google Scholar
Kannan, R., Cox, E., Wang, L., Kuzina, I., Gu, Q., & Giniger, E. (2018). Tyrosine phosphorylation and proteolytic cleavage of Notch are required for non-canonical Notch/Abl signaling in Drosophila axon guidance. Development,145(2), dev151548. https://doi.org/10.1242/dev.151548.
Article CAS PubMed PubMed Central Google Scholar
Karpova, A., Bar, J., & Kreutz, M. R. (2012). Long-distance signaling from synapse to nucleus via protein messengers. Advances in Experimental Medicine and Biology,970, 355–376. https://doi.org/10.1007/978-3-7091-0932-8_16.
Article CAS PubMed Google Scholar
Karpova, A., Mikhaylova, M., Bera, S., Bar, J., Reddy, P. P., Behnisch, T., et al. (2013). Encoding and transducing the synaptic or extrasynaptic origin of NMDA receptor signals to the nucleus. Cell,152(5), 1119–1133. https://doi.org/10.1016/j.cell.2013.02.002.
Article CAS PubMed Google Scholar
Kasuga, K., Kaneko, H., Nishizawa, M., Onodera, O., & Ikeuchi, T. (2007). Generation of intracellular domain of insulin receptor tyrosine kinase by gamma-secretase. Biochemical and Biophysical Research Communications,360(1), 90–96. https://doi.org/10.1016/j.bbrc.2007.06.022.
Article CAS PubMed Google Scholar
Ke, C., Gao, F., Tian, X., Li, C., Shi, D., He, W., et al. (2017). Slit2/Robo1 mediation of synaptic plasticity contributes to bone cancer pain. Molecular Neurobiology,54(1), 295–307. https://doi.org/10.1007/s12035-015-9564-9.
Article CAS PubMed Google Scholar
Kesten, D., Horovitz-Fried, M., Brutman-Barazani, T., & Sampson, S. R. (2018). Insulin-induced translocation of IR to the nucleus in insulin responsive cells requires a nuclear translocation sequence. Biochim Biophys Acta Mol Cell Res,1865(4), 551–559. https://doi.org/10.1016/j.bbamcr.2018.01.004.
Article CAS PubMed Google Scholar
Kidd, T., Brose, K., Mitchell, K. J., Fetter, R. D., Tessier-Lavigne, M., Goodman, C. S., et al. (1998). Roundabout controls axon crossing of the CNS midline and defines a novel subfamily of evolutionarily conserved guidance receptors. Cell,92(2), 205–215.
Article CAS Google Scholar
Kim, D. Y., Carey, B. W., Wang, H., Ingano, L. A., Binshtok, A. M., Wertz, M. H., et al. (2007). BACE1 regulates voltage-gated sodium channels and neuronal activity. Nature Cell Biology,9(7), 755–764. https://doi.org/10.1038/ncb1602.
Article CAS PubMed PubMed Central Google Scholar
Kim, J., Chang, A., Dudak, A., Federoff, H. J., & Lim, S. T. (2011). Characterization of nectin processing mediated by presenilin-dependent gamma-secretase. Journal of Neurochemistry,119(5), 945–956. https://doi.org/10.1111/j.1471-4159.2011.07479.x.
Article CAS PubMed PubMed Central Google Scholar
Kim, D. Y., Ingano, L. A., & Kovacs, D. M. (2002). Nectin-1alpha, an immunoglobulin-like receptor involved in the formation of synapses, is a substrate for presenilin/gamma-secretase-like cleavage. Journal of Biological Chemistry,277(51), 49976–49981. https://doi.org/10.1074/jbc.M210179200.
Article CAS PubMed Google Scholar
Kim, J., Lilliehook, C., Dudak, A., Prox, J., Saftig, P., Federoff, H. J., et al. (2010). Activity-dependent alpha-cleavage of nectin-1 is mediated by a disintegrin and metalloprotease 10 (ADAM10). Journal of Biological Chemistry,285(30), 22919–22926. https://doi.org/10.1074/jbc.M110.126649.
Article CAS PubMed Google Scholar
Kimberly, W. T., Zheng, J. B., Guenette, S. Y., & Selkoe, D. J. (2001). The intracellular domain of the beta-amyloid precursor protein is stabilized by Fe65 and translocates to the nucleus in a notch-like manner. Journal of Biological Chemistry,276(43), 40288–40292. https://doi.org/10.1074/jbc.C100447200.
Article CAS PubMed Google Scholar
Kimura, M., & Imamoto, N. (2014). Biological significance of the importin-beta family-dependent nucleocytoplasmic transport pathways. Traffic,15(7), 727–748. https://doi.org/10.1111/tra.12174.
Article CAS PubMed Google Scholar
Kinoshita, A., Shah, T., Tangredi, M. M., Strickland, D. K., & Hyman, B. T. (2003). The intracellular domain of the low density lipoprotein receptor-related protein modulates transactivation mediated by amyloid precursor protein and Fe65. Journal of Biological Chemistry,278(42), 41182–41188. https://doi.org/10.1074/jbc.M306403200.
Article CAS PubMed Google Scholar
Kiyota, T., & Kinoshita, T. (2004). The intracellular domain of X-Serrate-1 is cleaved and suppresses primary neurogenesis in Xenopus laevis. Mechanisms of Development,121(6), 573–585. https://doi.org/10.1016/j.mod.2004.03.034.
Article CAS PubMed Google Scholar
Klug, W., Dietl, A., Simon, B., Sinning, I., & Wild, K. (2011). Phosphorylation of LRP1 regulates the interaction with Fe65. FEBS Letters,585(20), 3229–3235. https://doi.org/10.1016/j.febslet.2011.09.028.
Article CAS PubMed Google Scholar
Knight, D., Iliadi, K., Charlton, M. P., Atwood, H. L., & Boulianne, G. L. (2007). Presynaptic plasticity and associative learning are impaired in a Drosophila presenilin null mutant. Developmental Neurobiology,67(12), 1598–1613. https://doi.org/10.1002/dneu.20532.
Article PubMed Google Scholar
Kohmura, N., Senzaki, K., Hamada, S., Kai, N., Yasuda, R., Watanabe, M., et al. (1998). Diversity revealed by a novel family of cadherins expressed in neurons at a synaptic complex. Neuron,20(6), 1137–1151.
Article CAS Google Scholar
Konietzko, U., Goodger, Z. V., Meyer, M., Kohli, B. M., Bosset, J., Lahiri, D. K., et al. (2010). Co-localization of the amyloid precursor protein and Notch intracellular domains in nuclear transcription factories. Neurobiology of Aging,31(1), 58–73. https://doi.org/10.1016/j.neurobiolaging.2008.03.001.
Article CAS PubMed Google Scholar
Kravchick, D. O., & Jordan, B. A. (2015). Presynapses go nuclear! EMBO Journal,34(8), 984–986. https://doi.org/10.15252/embj.201591331.
Article CAS PubMed Google Scholar
Krivosheya, D., Tapia, L., Levinson, J. N., Huang, K., Kang, Y., Hines, R., et al. (2008). ErbB4-neuregulin signaling modulates synapse development and dendritic arborization through distinct mechanisms. Journal of Biological Chemistry,283(47), 32944–32956. https://doi.org/10.1074/jbc.M800073200.
Article CAS PubMed Google Scholar
Lai, K. O., Zhao, Y., Ch’ng, T. H., & Martin, K. (2008). Importin-mediated retrograde transport of CREB2 from distal processes to the nucleus in neurons. Proceedings of the National Academy of Sciences USA,105(44), 17175–17180. https://doi.org/10.1073/pnas.0803906105.
Article Google Scholar
Lal, M., & Caplan, M. (2011). Regulated intramembrane proteolysis: Signaling pathways and biological functions. Physiology (Bethesda),26(1), 34–44. https://doi.org/10.1152/physiol.00028.2010.
Article CAS Google Scholar
Lalonde, R., Qian, S., & Strazielle, C. (2003). Transgenic mice expressing the PS1-A246E mutation: Effects on spatial learning, exploration, anxiety, and motor coordination. Behavioural Brain Research,138(1), 71–79.
Article CAS Google Scholar
Lammich, S., Okochi, M., Takeda, M., Kaether, C., Capell, A., Zimmer, A. K., et al. (2002). Presenilin-dependent intramembrane proteolysis of CD44 leads to the liberation of its intracellular domain and the secretion of an Abeta-like peptide. Journal of Biological Chemistry,277(47), 44754–44759. https://doi.org/10.1074/jbc.M206872200.
Article CAS PubMed Google Scholar
Lathia, J. D., Mattson, M. P., & Cheng, A. (2008). Notch: From neural development to neurological disorders. Journal of Neurochemistry,107(6), 1471–1481. https://doi.org/10.1111/j.1471-4159.2008.05715.x.
Article CAS PubMed PubMed Central Google Scholar
LaVoie, M. J., & Selkoe, D. J. (2003). The Notch ligands, Jagged and Delta, are sequentially processed by alpha-secretase and presenilin/gamma-secretase and release signaling fragments. Journal of Biological Chemistry,278(36), 34427–34437. https://doi.org/10.1074/jbc.M302659200.
Article CAS PubMed Google Scholar
Lee, S. H., Sharma, M., Sudhof, T. C., & Shen, J. (2014). Synaptic function of nicastrin in hippocampal neurons. Proceedings of the National Academy of Sciences USA,111(24), 8973–8978. https://doi.org/10.1073/pnas.1408554111.
Article CAS Google Scholar
Levi, S., Grady, R. M., Henry, M. D., Campbell, K. P., Sanes, J. R., & Craig, A. M. (2002). Dystroglycan is selectively associated with inhibitory GABAergic synapses but is dispensable for their differentiation. Journal of Neuroscience,22(11), 4274–4285.
Article CAS Google Scholar
Li, Y., Chen, Z., Gao, Y., Pan, G., Zheng, H., Zhang, Y., et al. (2017a). Synaptic adhesion molecule Pcdh-gammaC5 mediates synaptic dysfunction in Alzheimer’s disease. Journal of Neuroscience,37(38), 9259–9268. https://doi.org/10.1523/jneurosci.1051-17.2017.
Article CAS PubMed Google Scholar
Li, Y., Gao, Y., Xu, X., Shi, R., Liu, J., Yao, W., et al. (2017b). Slit2/Robo1 promotes synaptogenesis and functional recovery of spinal cord injury. NeuroReport,28(2), 75–81. https://doi.org/10.1097/wnr.0000000000000715.
Article PubMed Google Scholar
Li, Q., Vo, H. T., Wang, J., Fox-Quick, S., Dobrunz, L. E., & King, G. D. (2017c). Klotho regulates CA1 hippocampal synaptic plasticity. Neuroscience,347, 123–133. https://doi.org/10.1016/j.neuroscience.2017.02.006.
Article CAS PubMed PubMed Central Google Scholar
Li, B., Woo, R. S., Mei, L., & Malinow, R. (2007). The neuregulin-1 receptor erbB4 controls glutamatergic synapse maturation and plasticity. Neuron,54(4), 583–597. https://doi.org/10.1016/j.neuron.2007.03.028.
Article CAS PubMed PubMed Central Google Scholar
Lichtenthaler, S. F., Haass, C., & Steiner, H. (2011). Regulated intramembrane proteolysis–lessons from amyloid precursor protein processing. Journal of Neurochemistry,117(5), 779–796. https://doi.org/10.1111/j.1471-4159.2011.07248.x.
Article CAS PubMed Google Scholar
Lichtenthaler, S. F., Lemberg, M. K., & Fluhrer, R. (2018). Proteolytic ectodomain shedding of membrane proteins in mammals-hardware, concepts, and recent developments. The Embo Journal,37(15), 99456. https://doi.org/10.15252/embj.201899456.
Article CAS Google Scholar
Lim, A. F., Lim, W. L., & Ch’ng, T. H. (2017). Activity-dependent synapse to nucleus signaling. Neurobiology of Learning and Memory,138, 78–84. https://doi.org/10.1016/j.nlm.2016.07.024.
Article CAS PubMed Google Scholar
Lim, S. T., Lim, K. C., Giuliano, R. E., & Federoff, H. J. (2008). Temporal and spatial localization of nectin-1 and l-afadin during synaptogenesis in hippocampal neurons. Journal of Comparative Neurology,507(2), 1228–1244. https://doi.org/10.1002/cne.21608.
Article CAS PubMed Google Scholar
Lin, K. T., Sloniowski, S., Ethell, D. W., & Ethell, I. M. (2008). Ephrin-B2-induced cleavage of EphB2 receptor is mediated by matrix metalloproteinases to trigger cell repulsion. Journal of Biological Chemistry,283(43), 28969–28979. https://doi.org/10.1074/jbc.M804401200.
Article CAS PubMed Google Scholar
Litterst, C., Georgakopoulos, A., Shioi, J., Ghersi, E., Wisniewski, T., Wang, R., et al. (2007). Ligand binding and calcium influx induce distinct ectodomain/gamma-secretase-processing pathways of EphB2 receptor. Journal of Biological Chemistry,282(22), 16155–16163. https://doi.org/10.1074/jbc.M611449200.
Article CAS PubMed Google Scholar
Liu, S., Wang, Y., Worley, P. F., Mattson, M. P., & Gaiano, N. (2015). The canonical Notch pathway effector RBP-J regulates neuronal plasticity and expression of GABA transporters in hippocampal networks. Hippocampus,25(5), 670–678. https://doi.org/10.1002/hipo.22402.
Article CAS PubMed PubMed Central Google Scholar
Liu, A., Zhou, Z., Dang, R., Zhu, Y., Qi, J., He, G., et al. (2016). Neuroligin 1 regulates spines and synaptic plasticity via LIMK1/cofilin-mediated actin reorganization. Journal of Cell Biology,212(4), 449–463. https://doi.org/10.1083/jcb.201509023.
Article CAS PubMed Google Scholar
Lozsadi, D. A., & Larner, A. J. (2006). Prevalence and causes of seizures at the time of diagnosis of probable Alzheimer’s disease. Dementia and Geriatric Cognitive Disorders,22(2), 121–124. https://doi.org/10.1159/000093664.
Article CAS PubMed Google Scholar
Lutz, D., Wolters-Eisfeld, G., Schachner, M., & Kleene, R. (2014). Cathepsin E generates a sumoylated intracellular fragment of the cell adhesion molecule L1 to promote neuronal and Schwann cell migration as well as myelination. Journal of Neurochemistry,128(5), 713–724. https://doi.org/10.1111/jnc.12473.
Article CAS PubMed Google Scholar
Marambaud, P., Wen, P. H., Dutt, A., Shioi, J., Takashima, A., Siman, R., et al. (2003). A CBP binding transcriptional repressor produced by the PS1/epsilon-cleavage of N-cadherin is inhibited by PS1 FAD mutations. Cell,114(5), 635–645.
Article CAS Google Scholar
Maretzky, T., Schulte, M., Ludwig, A., Rose-John, S., Blobel, C., Hartmann, D., et al. (2005). L1 is sequentially processed by two differently activated metalloproteases and presenilin/gamma-secretase and regulates neural cell adhesion, cell migration, and neurite outgrowth. Molecular and Cellular Biology,25(20), 9040–9053. https://doi.org/10.1128/mcb.25.20.9040-9053.2005.
Article CAS PubMed PubMed Central Google Scholar
Martin, L., Fluhrer, R., Reiss, K., Kremmer, E., Saftig, P., & Haass, C. (2008). Regulated intramembrane proteolysis of Bri2 (Itm2b) by ADAM10 and SPPL2a/SPPL2b. Journal of Biological Chemistry,283(3), 1644–1652. https://doi.org/10.1074/jbc.M706661200.
Article CAS PubMed Google Scholar
Martins, F., Marafona, A. M., Pereira, C. D., Muller, T., Loosse, C., Kolbe, K., et al. (2018). Identification and characterization of the BRI2 interactome in the brain. Science Reports,8(1), 3548. https://doi.org/10.1038/s41598-018-21453-3.
Article CAS Google Scholar
Martins, F., Rebelo, S., Santos, M., Cotrim, C. Z., da Cruz e Silva, E. F., & da Cruz e Silva, O. A. (2016). BRI2 and BRI3 are functionally distinct phosphoproteins. Cellular Signalling,28(1), 130–144. https://doi.org/10.1016/j.cellsig.2015.10.012.
Article CAS PubMed Google Scholar
Mata-Balaguer, T., Cuchillo-Ibanez, I., Calero, M., Ferrer, I., & Saez-Valero, J. (2018). Decreased generation of C-terminal fragments of ApoER2 and increased reelin expression in Alzheimer’s disease. The FASEB Journal,32(7), 3536–3546. https://doi.org/10.1096/fj.201700736RR.
Article CAS PubMed Google Scholar
Matsui, C., Inoue, E., Kakita, A., Arita, K., Deguchi-Tawarada, M., Togawa, A., et al. (2012). Involvement of the gamma-secretase-mediated EphA4 signaling pathway in synaptic pathogenesis of Alzheimer’s disease. Brain Pathology,22(6), 776–787. https://doi.org/10.1111/j.1750-3639.2012.00587.x.
Article CAS PubMed Google Scholar
Matusica, D., Skeldal, S., Sykes, A. M., Palstra, N., Sharma, A., & Coulson, E. J. (2013). An intracellular domain fragment of the p75 neurotrophin receptor (p75(NTR)) enhances tropomyosin receptor kinase A (TrkA) receptor function. Journal of Biological Chemistry,288(16), 11144–11154. https://doi.org/10.1074/jbc.M112.436469.
Article CAS PubMed Google Scholar
May, P., Rohlmann, A., Bock, H. H., Zurhove, K., Marth, J. D., Schomburg, E. D., et al. (2004). Neuronal LRP1 functionally associates with postsynaptic proteins and is required for normal motor function in mice. Molecular and Cellular Biology,24(20), 8872–8883. https://doi.org/10.1128/mcb.24.20.8872-8883.2004.
Article CAS PubMed PubMed Central Google Scholar
McCarthy, A. J., Coleman-Vaughan, C., & McCarthy, J. V. (2017). Regulated intramembrane proteolysis: Emergent role in cell signalling pathways. Biochemical Society Transactions,45(6), 1185–1202. https://doi.org/10.1042/bst20170002.
Article CAS PubMed Google Scholar
McClelland, A. C., Sheffler-Collins, S. I., Kayser, M. S., & Dalva, M. B. (2009). Ephrin-B1 and ephrin-B2 mediate EphB-dependent presynaptic development via syntenin-1. Proceedings of the National Academy of Sciences USA,106(48), 20487–20492. https://doi.org/10.1073/pnas.0811862106.
Article Google Scholar
McElroy, B., Powell, J. C., & McCarthy, J. V. (2007). The insulin-like growth factor 1 (IGF-1) receptor is a substrate for gamma-secretase-mediated intramembrane proteolysis. Biochemical and Biophysical Research Communications,358(4), 1136–1141. https://doi.org/10.1016/j.bbrc.2007.05.062.
Article CAS PubMed Google Scholar
Meckler, X., & Checler, F. (2016). Presenilin 1 and presenilin 2 target gamma-secretase complexes to distinct cellular compartments. Journal of Biological Chemistry,291(24), 12821–12837. https://doi.org/10.1074/jbc.M115.708297.
Article CAS PubMed Google Scholar
Mei, L., & Nave, K. A. (2014). Neuregulin-ERBB signaling in the nervous system and neuropsychiatric diseases. Neuron,83(1), 27–49. https://doi.org/10.1016/j.neuron.2014.06.007.
Article CAS PubMed PubMed Central Google Scholar
Mei, L., & Xiong, W. C. (2008). Neuregulin 1 in neural development, synaptic plasticity and schizophrenia. Nature Reviews Neuroscience,9(6), 437–452. https://doi.org/10.1038/nrn2392.
Article CAS PubMed PubMed Central Google Scholar
Mentrup, T., Fluhrer, R., & Schroder, B. (2017a). Latest emerging functions of SPP/SPPL intramembrane proteases. European Journal of Cell Biology,96(5), 372–382. https://doi.org/10.1016/j.ejcb.2017.03.002.
Article CAS PubMed Google Scholar
Mentrup, T., Hasler, R., Fluhrer, R., Saftig, P., & Schroder, B. (2015). A cell-based assay reveals nuclear translocation of intracellular domains released by SPPL proteases. Traffic,16(8), 871–892. https://doi.org/10.1111/tra.12287.
Article CAS PubMed Google Scholar
Mentrup, T., Loock, A. C., Fluhrer, R., & Schroder, B. (2017b). Signal peptide peptidase and SPP-like proteases—Possible therapeutic targets? Biochim Biophys Acta Molecular Cell Research,1864(11 Pt B), 2169–2182. https://doi.org/10.1016/j.bbamcr.2017.06.007.
Article CAS PubMed Google Scholar
Miletti-Gonzalez, K. E., Murphy, K., Kumaran, M. N., Ravindranath, A. K., Wernyj, R. P., Kaur, S., et al. (2012). Identification of function for CD44 intracytoplasmic domain (CD44-ICD): Modulation of matrix metalloproteinase 9 (MMP-9) transcription via novel promoter response element. Journal of Biological Chemistry,287(23), 18995–19007. https://doi.org/10.1074/jbc.M111.318774.
Article CAS PubMed Google Scholar
Mosca, T. J., & Schwarz, T. L. (2010). Drosophila Importin-alpha2 is involved in synapse, axon and muscle development. PLoS ONE,5(12), e15223. https://doi.org/10.1371/journal.pone.0015223.
Article CAS PubMed PubMed Central Google Scholar
Multhaup, G., Huber, O., Buee, L., & Galas, M. C. (2015). Amyloid precursor protein (APP) metabolites APP intracellular fragment (AICD), Abeta42, and Tau in nuclear roles. Journal of Biological Chemistry,290(39), 23515–23522. https://doi.org/10.1074/jbc.R115.677211.
Article CAS PubMed Google Scholar
Murata, Y., Hamada, S., Morishita, H., Mutoh, T., & Yagi, T. (2004). Interaction with protocadherin-gamma regulates the cell surface expression of protocadherin-alpha. Journal of Biological Chemistry,279(47), 49508–49516. https://doi.org/10.1074/jbc.M408771200.
Article CAS PubMed Google Scholar
Nagara, Y., Hagiyama, M., Hatano, N., Futai, E., Suo, S., Takaoka, Y., et al. (2012). Tumor suppressor cell adhesion molecule 1 (CADM1) is cleaved by a disintegrin and metalloprotease 10 (ADAM10) and subsequently cleaved by gamma-secretase complex. Biochemical and Biophysical Research Communications,417(1), 462–467. https://doi.org/10.1016/j.bbrc.2011.11.140.
Article CAS PubMed Google Scholar
Nakajima, C., Kulik, A., Frotscher, M., Herz, J., Schafer, M., Bock, H. H., et al. (2013). Low density lipoprotein receptor-related protein 1 (LRP1) modulates N-methyl-D-aspartate (NMDA) receptor-dependent intracellular signaling and NMDA-induced regulation of postsynaptic protein complexes. Journal of Biological Chemistry,288(30), 21909–21923. https://doi.org/10.1074/jbc.M112.444364.
Article CAS PubMed Google Scholar
Nakajo, H., Ishibashi, K., Aoyama, K., Kubota, S., Hasegawa, H., Yamaguchi, N., et al. (2019). Role for tyrosine phosphorylation of SUV39H1 histone methyltransferase in enhanced trimethylation of histone H3K9 via neuregulin-1/ErbB4 nuclear signaling. Biochemical and Biophysical Research Communications,511(4), 765–771. https://doi.org/10.1016/j.bbrc.2019.02.130.
Article CAS PubMed Google Scholar
Nakaya, T., & Suzuki, T. (2006). Role of APP phosphorylation in FE65-dependent gene transactivation mediated by AICD. Genes to Cells,11(6), 633–645. https://doi.org/10.1111/j.1365-2443.2006.00968.x.
Article CAS PubMed Google Scholar
Nakayama, K., Ohkawara, T., Hiratochi, M., Koh, C. S., & Nagase, H. (2008). The intracellular domain of amyloid precursor protein induces neuron-specific apoptosis. Neuroscience Letters,444(2), 127–131. https://doi.org/10.1016/j.neulet.2008.08.034.
Article CAS PubMed Google Scholar
Nam, S. H., Seo, S. J., Goo, J. S., Kim, J. E., Choi, S. I., Lee, H. R., et al. (2011). Pen-2 overexpression induces Abeta-42 production, memory defect, motor activity enhancement and feeding behavior dysfunction in NSE/Pen-2 transgenic mice. International Journal of Molecular Medicine,28(6), 961–971. https://doi.org/10.3892/ijmm.2011.767.
Article CAS PubMed Google Scholar
Naresh, A., Long, W., Vidal, G. A., Wimley, W. C., Marrero, L., Sartor, C. I., et al. (2006). The ERBB4/HER4 intracellular domain 4ICD is a BH3-only protein promoting apoptosis of breast cancer cells. Cancer Research,66(12), 6412–6420. https://doi.org/10.1158/0008-5472.can-05-2368.
Article CAS PubMed Google Scholar
Neuhaus-Follini, A., & Bashaw, G. J. (2015). The intracellular domain of the frazzled/DCC receptor is a transcription factor required for commissural axon guidance. Neuron,87(4), 751–763. https://doi.org/10.1016/j.neuron.2015.08.006.
Article CAS PubMed PubMed Central Google Scholar
Nhan, H. S., Chiang, K., & Koo, E. H. (2015). The multifaceted nature of amyloid precursor protein and its proteolytic fragments: Friends and foes. Acta Neuropathologica,129(1), 1–19. https://doi.org/10.1007/s00401-014-1347-2.
Article CAS PubMed Google Scholar
Niwa, M., Sidrauski, C., Kaufman, R. J., & Walter, P. (1999). A role for presenilin-1 in nuclear accumulation of Ire1 fragments and induction of the mammalian unfolded protein response. Cell,99(7), 691–702.
Article CAS Google Scholar
Nyborg, A. C., Ladd, T. B., Zwizinski, C. W., Lah, J. J., & Golde, T. E. (2006). Sortilin, SorCS1b, and SorLA Vps10p sorting receptors, are novel gamma-secretase substrates. Molecular Neurodegeneration,1, 3. https://doi.org/10.1186/1750-1326-1-3.
Article CAS PubMed PubMed Central Google Scholar
Oblander, S. A., Ensslen-Craig, S. E., Longo, F. M., & Brady-Kalnay, S. M. (2007). E-cadherin promotes retinal ganglion cell neurite outgrowth in a protein tyrosine phosphatase-mu-dependent manner. Molecular and Cellular Neuroscience,34(3), 481–492. https://doi.org/10.1016/j.mcn.2006.12.002.
Article CAS PubMed Google Scholar
Pardossi-Piquard, R., & Checler, F. (2012). The physiology of the beta-amyloid precursor protein intracellular domain AICD. Journal of Neurochemistry,120(Suppl 1), 109–124. https://doi.org/10.1111/j.1471-4159.2011.07475.x.
Article CAS PubMed Google Scholar
Pardossi-Piquard, R., Petit, A., Kawarai, T., Sunyach, C., Alves da Costa, C., Vincent, B., et al. (2005). Presenilin-dependent transcriptional control of the Abeta-degrading enzyme neprilysin by intracellular domains of betaAPP and APLP. Neuron,46(4), 541–554. https://doi.org/10.1016/j.neuron.2005.04.008.
Article CAS PubMed Google Scholar
Parkhurst, C. N., Zampieri, N., & Chao, M. V. (2010). Nuclear localization of the p75 neurotrophin receptor intracellular domain. Journal of Biological Chemistry,285(8), 5361–5368. https://doi.org/10.1074/jbc.M109.045054.
Article CAS PubMed Google Scholar
Parra, L. M., Hartmann, M., Schubach, S., Li, Y., Herrlich, P., & Herrlich, A. (2015). Distinct intracellular domain substrate modifications selectively regulate ectodomain cleavage of NRG1 or CD44. Molecular and Cellular Biology,35(19), 3381–3395. https://doi.org/10.1128/mcb.00500-15.
Article CAS PubMed PubMed Central Google Scholar
Paschkowsky, S., Oestereich, F., & Munter, L. M. (2018). Embedded in the membrane: How lipids confer activity and specificity to intramembrane proteases. Journal of Membrane Biology,251(3), 369–378. https://doi.org/10.1007/s00232-017-0008-5.
Article CAS PubMed Google Scholar
Pathak, A., Stanley, E. M., Hickman, F. E., Wallace, N., Brewer, B., Li, D., et al. (2018). Retrograde degenerative signaling mediated by the p75 neurotrophin receptor requires p150(Glued) deacetylation by axonal HDAC1. Developmental Cell,46(3), 376–387.e377. https://doi.org/10.1016/j.devcel.2018.07.001.
Article CAS PubMed PubMed Central Google Scholar
Peixoto, R. T., Kunz, P. A., Kwon, H., Mabb, A. M., Sabatini, B. L., Philpot, B. D., et al. (2012). Transsynaptic signaling by activity-dependent cleavage of neuroligin-1. Neuron,76(2), 396–409. https://doi.org/10.1016/j.neuron.2012.07.006.
Article CAS PubMed PubMed Central Google Scholar
Perry, R. B., Doron-Mandel, E., Iavnilovitch, E., Rishal, I., Dagan, S. Y., Tsoory, M., et al. (2012). Subcellular knockout of importin beta1 perturbs axonal retrograde signaling. Neuron,75(2), 294–305. https://doi.org/10.1016/j.neuron.2012.05.033.
Article CAS PubMed PubMed Central Google Scholar
Phillips, G. R., Tanaka, H., Frank, M., Elste, A., Fidler, L., Benson, D. L., et al. (2003). Gamma-protocadherins are targeted to subsets of synapses and intracellular organelles in neurons. Journal of Neuroscience,23(12), 5096–5104.
Article CAS Google Scholar
Piao, Y., Kimura, A., Urano, S., Saito, Y., Taru, H., Yamamoto, T., et al. (2013). Mechanism of intramembrane cleavage of alcadeins by gamma-secretase. PLoS ONE,8(4), e62431. https://doi.org/10.1371/journal.pone.0062431.
Article CAS PubMed PubMed Central Google Scholar
Pierfelice, T., Alberi, L., & Gaiano, N. (2011). Notch in the vertebrate nervous system: An old dog with new tricks. Neuron,69(5), 840–855. https://doi.org/10.1016/j.neuron.2011.02.031.
Article CAS PubMed Google Scholar
Podlesniy, P., Kichev, A., Pedraza, C., Saurat, J., Encinas, M., Perez, B., et al. (2006). Pro-NGF from Alzheimer’s disease and normal human brain displays distinctive abilities to induce processing and nuclear translocation of intracellular domain of p75NTR and apoptosis. American Journal of Pathology,169(1), 119–131. https://doi.org/10.2353/ajpath.2006.050787.
Article CAS PubMed Google Scholar
Poreba, M., Szalek, A., Rut, W., Kasperkiewicz, P., Rutkowska-Wlodarczyk, I., Snipas, S. J., et al. (2017). Highly sensitive and adaptable fluorescence-quenched pair discloses the substrate specificity profiles in diverse protease families. Science Reports,7, 43135. https://doi.org/10.1038/srep43135.
Article CAS Google Scholar
Pribiag, H., Peng, H., Shah, W. A., Stellwagen, D., & Carbonetto, S. (2014). Dystroglycan mediates homeostatic synaptic plasticity at GABAergic synapses. Proceedings of the National Academy of Sciences USA,111(18), 6810–6815. https://doi.org/10.1073/pnas.1321774111.
Article CAS Google Scholar
Rawson, R. B. (2003). Control of lipid metabolism by regulated intramembrane proteolysis of sterol regulatory element binding proteins (SREBPs). Biochemical Society Symposia,70, 221–231.
Article CAS Google Scholar
Restituito, S., Khatri, L., Ninan, I., Mathews, P. M., Liu, X., Weinberg, R. J., et al. (2011). Synaptic autoregulation by metalloproteases and gamma-secretase. Journal of Neuroscience,31(34), 12083–12093. https://doi.org/10.1523/jneurosci.2513-11.2011.
Article CAS PubMed Google Scholar
Rico, B., & Marin, O. (2011). Neuregulin signaling, cortical circuitry development and schizophrenia. Current Opinion in Genetics & Development,21(3), 262–270. https://doi.org/10.1016/j.gde.2010.12.010.
Article CAS Google Scholar
Riedle, S., Kiefel, H., Gast, D., Bondong, S., Wolterink, S., Gutwein, P., et al. (2009). Nuclear translocation and signalling of L1-CAM in human carcinoma cells requires ADAM10 and presenilin/gamma-secretase activity. Biochemical Journal,420(3), 391–402. https://doi.org/10.1042/bj20081625.
Article CAS PubMed PubMed Central Google Scholar
Rosenstein, J. M., Mani, N., Khaibullina, A., & Krum, J. M. (2003). Neurotrophic effects of vascular endothelial growth factor on organotypic cortical explants and primary cortical neurons. Journal of Neuroscience,23(35), 11036–11044.
Article CAS Google Scholar
Roszkowska, M., Skupien, A., Wojtowicz, T., Konopka, A., Gorlewicz, A., Kisiel, M., et al. (2016). CD44: A novel synaptic cell adhesion molecule regulating structural and functional plasticity of dendritic spines. Molecular Biology of the Cell,27(25), 4055–4066. https://doi.org/10.1091/mbc.E16-06-0423.
Article CAS PubMed PubMed Central Google Scholar
Roth, D. M., Moseley, G. W., Pouton, C. W., & Jans, D. A. (2011). Mechanism of microtubule-facilitated “fast track” nuclear import. Journal of Biological Chemistry,286(16), 14335–14351. https://doi.org/10.1074/jbc.M110.210302.
Article CAS PubMed Google Scholar
Sachse, C. C., Kim, Y. H., Agsten, M., Huth, T., Alzheimer, C., Kovacs, D. M., et al. (2013). BACE1 and presenilin/gamma-secretase regulate proteolytic processing of KCNE1 and 2, auxiliary subunits of voltage-gated potassium channels. The FASEB Journal,27(6), 2458–2467. https://doi.org/10.1096/fj.12-214056.
Article CAS PubMed PubMed Central Google Scholar
Sachse, S. M., Lievens, S., Ribeiro, L. F., Dascenco, D., Masschaele, D., Horre, K., et al. (2019). Nuclear import of the DSCAM-cytoplasmic domain drives signaling capable of inhibiting synapse formation. EMBO Journal,38(6), e99669. https://doi.org/10.15252/embj.201899669.
Article CAS PubMed Google Scholar
Saito, A., Cai, L., Matsuhisa, K., Ohtake, Y., Kaneko, M., Kanemoto, S., et al. (2018). Neuronal activity-dependent local activation of dendritic unfolded protein response promotes expression of brain-derived neurotrophic factor in cell soma. Journal of Neurochemistry,144(1), 35–49. https://doi.org/10.1111/jnc.14221.
Article CAS PubMed Google Scholar
Sardi, S. P., Murtie, J., Koirala, S., Patten, B. A., & Corfas, G. (2006). Presenilin-dependent ErbB4 nuclear signaling regulates the timing of astrogenesis in the developing brain. Cell,127(1), 185–197. https://doi.org/10.1016/j.cell.2006.07.037.
Article CAS PubMed Google Scholar
Saura, C. A., Servian-Morilla, E., & Scholl, F. G. (2011). Presenilin/gamma-secretase regulates neurexin processing at synapses. PLoS ONE,6(4), e19430. https://doi.org/10.1371/journal.pone.0019430.
Article CAS PubMed PubMed Central Google Scholar
Schedin-Weiss, S., Caesar, I., Winblad, B., Blom, H., & Tjernberg, L. O. (2016). Super-resolution microscopy reveals gamma-secretase at both sides of the neuronal synapse. Acta Neuropathologica Communications,4, 29. https://doi.org/10.1186/s40478-016-0296-5.
Article CAS PubMed PubMed Central Google Scholar
Scheinfeld, M. H., Ghersi, E., Laky, K., Fowlkes, B. J., & D’Adamio, L. (2002). Processing of beta-amyloid precursor-like protein-1 and -2 by gamma-secretase regulates transcription. Journal of Biological Chemistry,277(46), 44195–44201. https://doi.org/10.1074/jbc.M208110200.
Article CAS PubMed Google Scholar
Schilling, S., Mehr, A., Ludewig, S., Stephan, J., Zimmermann, M., August, A., et al. (2017). APLP1 is a synaptic cell adhesion molecule, supporting maintenance of dendritic spines and basal synaptic transmission. Journal of Neuroscience,37(21), 5345–5365. https://doi.org/10.1523/jneurosci.1875-16.2017.
Article CAS PubMed Google Scholar
Schulz, J. G., Annaert, W., Vandekerckhove, J., Zimmermann, P., De Strooper, B., & David, G. (2003). Syndecan 3 intramembrane proteolysis is presenilin/gamma-secretase-dependent and modulates cytosolic signaling. Journal of Biological Chemistry,278(49), 48651–48657. https://doi.org/10.1074/jbc.M308424200.
Article CAS PubMed Google Scholar
Seki, M., Watanabe, A., Enomoto, S., Kawamura, T., Ito, H., Kodama, T., et al. (2010). Human ROBO1 is cleaved by metalloproteinases and gamma-secretase and migrates to the nucleus in cancer cells. FEBS Letters,584(13), 2909–2915. https://doi.org/10.1016/j.febslet.2010.05.009.
Article CAS PubMed Google Scholar
Shamir, A., Kwon, O. B., Karavanova, I., Vullhorst, D., Leiva-Salcedo, E., Janssen, M. J., et al. (2012). The importance of the NRG-1/ErbB4 pathway for synaptic plasticity and behaviors associated with psychiatric disorders. Journal of Neuroscience,32(9), 2988–2997. https://doi.org/10.1523/jneurosci.1899-11.2012.
Article CAS PubMed Google Scholar
Shintani, T., & Noda, M. (2008). Functions of receptor-type protein tyrosine phosphatase in the formation of retinal projection. Seikagaku,80(8), 733–742.
CAS PubMed Google Scholar
Six, E., Ndiaye, D., Laabi, Y., Brou, C., Gupta-Rossi, N., Israel, A., et al. (2003). The Notch ligand Delta1 is sequentially cleaved by an ADAM protease and gamma-secretase. Proceedings of the National Academy of Sciences USA,100(13), 7638–7643. https://doi.org/10.1073/pnas.1230693100.
Article CAS Google Scholar
Smith, H. M., & Raikhel, N. V. (1998). Nuclear localization signal receptor importin alpha associates with the cytoskeleton. Plant Cell,10(11), 1791–1799.
CAS PubMed PubMed Central Google Scholar
Song, Y. S., Lee, H. J., Prosselkov, P., Itohara, S., & Kim, E. (2013). Trans-induced cis interaction in the tripartite NGL-1, netrin-G1 and LAR adhesion complex promotes development of excitatory synapses. Journal of Cell Science,126(Pt 21), 4926–4938. https://doi.org/10.1242/jcs.129718.
Article CAS PubMed Google Scholar
Sudhof, T. C. (2017). Synaptic neurexin complexes: A molecular code for the logic of neural circuits. Cell,171(4), 745–769. https://doi.org/10.1016/j.cell.2017.10.024.
Article CAS PubMed PubMed Central Google Scholar
Sun, X., Beglopoulos, V., Mattson, M. P., & Shen, J. (2005). Hippocampal spatial memory impairments caused by the familial Alzheimer’s disease-linked presenilin 1 M146 V mutation. Neurodegenerative Disease,2(1), 6–15. https://doi.org/10.1159/000086426.
Article CAS Google Scholar
Suzuki, K., Hayashi, Y., Nakahara, S., Kumazaki, H., Prox, J., Horiuchi, K., et al. (2012). Activity-dependent proteolytic cleavage of neuroligin-1. Neuron,76(2), 410–422. https://doi.org/10.1016/j.neuron.2012.10.003.
Article CAS PubMed Google Scholar
Takei, N., Sobu, Y., Kimura, A., Urano, S., Piao, Y., Araki, Y., et al. (2015). Cytoplasmic fragment of Alcadein alpha generated by regulated intramembrane proteolysis enhances amyloid beta-protein precursor (APP) transport into the late secretory pathway and facilitates APP cleavage. Journal of Biological Chemistry,290(2), 987–995. https://doi.org/10.1074/jbc.M114.599852.
Article CAS PubMed Google Scholar
Tamura, H., Fukada, M., Fujikawa, A., & Noda, M. (2006). Protein tyrosine phosphatase receptor type Z is involved in hippocampus-dependent memory formation through dephosphorylation at Y1105 on p190 RhoGAP. Neuroscience Letters,399(1–2), 33–38. https://doi.org/10.1016/j.neulet.2006.01.045.
Article CAS PubMed Google Scholar
Taniguchi, Y., Kim, S. H., & Sisodia, S. S. (2003). Presenilin-dependent “gamma-secretase” processing of deleted in colorectal cancer (DCC). Journal of Biological Chemistry,278(33), 30425–30428. https://doi.org/10.1074/jbc.C300239200.
Article CAS PubMed Google Scholar
Tcherkezian, J., Brittis, P. A., Thomas, F., Roux, P. P., & Flanagan, J. G. (2010). Transmembrane receptor DCC associates with protein synthesis machinery and regulates translation. Cell,141(4), 632–644. https://doi.org/10.1016/j.cell.2010.04.008.
Article CAS PubMed PubMed Central Google Scholar
Telese, F., Ma, Q., Perez, P. M., Notani, D., Oh, S., Li, W., et al. (2015). LRP8-reelin-regulated neuronal enhancer signature underlying learning and memory formation. Neuron,86(3), 696–710. https://doi.org/10.1016/j.neuron.2015.03.033.
Article CAS PubMed PubMed Central Google Scholar
Thompson, K. R., Otis, K. O., Chen, D. Y., Zhao, Y., O’Dell, T. J., & Martin, K. C. (2004). Synapse to nucleus signaling during long-term synaptic plasticity; a role for the classical active nuclear import pathway. Neuron,44(6), 997–1009. https://doi.org/10.1016/j.neuron.2004.11.025.
Article CAS PubMed Google Scholar
Tisi, M. A., Xie, Y., Yeo, T. T., & Longo, F. M. (2000). Downregulation of LAR tyrosine phosphatase prevents apoptosis and augments NGF-induced neurite outgrowth. Journal of Neurobiology,42(4), 477–486.
Article CAS Google Scholar
Tomita, T., Tanaka, S., Morohashi, Y., & Iwatsubo, T. (2006). Presenilin-dependent intramembrane cleavage of ephrin-B1. Molecular Neurodegeneration,1, 2. https://doi.org/10.1186/1750-1326-1-2.
Article CAS PubMed PubMed Central Google Scholar
Triana-Baltzer, G. B., Liu, Z., Gounko, N. V., & Berg, D. K. (2008). Multiple cell adhesion molecules shaping a complex nicotinic synapse on neurons. Molecular and Cellular Neuroscience,39(1), 74–82. https://doi.org/10.1016/j.mcn.2008.05.017.
Article CAS PubMed Google Scholar
Trillaud-Doppia, E., & Boehm, J. (2018). The amyloid precursor protein intracellular domain is an effector molecule of metaplasticity. Biological Psychiatry,83(5), 406–415. https://doi.org/10.1016/j.biopsych.2016.12.015.
Article CAS PubMed Google Scholar
Tu, M., Zhu, P., Hu, S., Wang, W., Su, Z., Guan, J., et al. (2017). Notch1 signaling activation contributes to adult hippocampal neurogenesis following traumatic brain injury. Medical Science Monitor,23, 5480–5487.
Article CAS Google Scholar
Underwood, C. K., & Coulson, E. J. (2008). The p75 neurotrophin receptor. International Journal of Biochemistry & Cell Biology,40(9), 1664–1668. https://doi.org/10.1016/j.biocel.2007.06.010.
Article CAS Google Scholar
Vasquez-Limeta, A., Wagstaff, K. M., Ortega, A., Crouch, D. H., Jans, D. A., & Cisneros, B. (2014). Nuclear import of beta-dystroglycan is facilitated by ezrin-mediated cytoskeleton reorganization. PLoS ONE,9(3), e90629. https://doi.org/10.1371/journal.pone.0090629.
Article CAS PubMed PubMed Central Google Scholar
Vicario, A., Kisiswa, L., Tann, J. Y., Kelly, C. E., & Ibanez, C. F. (2015). Neuron-type-specific signaling by the p75NTR death receptor is regulated by differential proteolytic cleavage. Journal of Cell Science,128(8), 1507–1517. https://doi.org/10.1242/jcs.161745.
Article CAS PubMed Google Scholar
Vogt, L., Schrimpf, S. P., Meskenaite, V., Frischknecht, R., Kinter, J., Leone, D. P., et al. (2001). Calsyntenin-1, a proteolytically processed postsynaptic membrane protein with a cytoplasmic calcium-binding domain. Molecular and Cellular Neuroscience,17(1), 151–166. https://doi.org/10.1006/mcne.2000.0937.
Article CAS PubMed Google Scholar
Vogt, D. L., Thomas, D., Galvan, V., Bredesen, D. E., Lamb, B. T., & Pimplikar, S. W. (2011). Abnormal neuronal networks and seizure susceptibility in mice overexpressing the APP intracellular domain. Neurobiology of Aging,32(9), 1725–1729. https://doi.org/10.1016/j.neurobiolaging.2009.09.002.
Article CAS PubMed Google Scholar
Wagstaff, K. M., & Jans, D. A. (2009). Importins and beyond: Non-conventional nuclear transport mechanisms. Traffic,10(9), 1188–1198. https://doi.org/10.1111/j.1600-0854.2009.00937.x.
Article CAS PubMed Google Scholar
Waldron, E., Isbert, S., Kern, A., Jaeger, S., Martin, A. M., Hebert, S. S., et al. (2008). Increased AICD generation does not result in increased nuclear translocation or activation of target gene transcription. Experimental Cell Research,314(13), 2419–2433. https://doi.org/10.1016/j.yexcr.2008.05.003.
Article CAS PubMed Google Scholar
Walsh, D. M., Fadeeva, J. V., LaVoie, M. J., Paliga, K., Eggert, S., Kimberly, W. T., et al. (2003). gamma-Secretase cleavage and binding to FE65 regulate the nuclear translocation of the intracellular C-terminal domain (ICD) of the APP family of proteins. Biochemistry,42(22), 6664–6673. https://doi.org/10.1021/bi027375c.
Article CAS PubMed Google Scholar
Waschbusch, D., Born, S., Niediek, V., Kirchgessner, N., Tamboli, I. Y., Walter, J., et al. (2009). Presenilin 1 affects focal adhesion site formation and cell force generation via c-Src transcriptional and posttranslational regulation. Journal of Biological Chemistry,284(15), 10138–10149. https://doi.org/10.1074/jbc.M806825200.
Article CAS PubMed Google Scholar
Weinmaster, G. (2000). Notch signal transduction: A real rip and more. Current Opinion in Genetics & Development,10(4), 363–369.
Article CAS Google Scholar
Wiegert, J. S., Bengtson, C. P., & Bading, H. (2007). Diffusion and not active transport underlies and limits ERK1/2 synapse-to-nucleus signaling in hippocampal neurons. Journal of Biological Chemistry,282(40), 29621–29633. https://doi.org/10.1074/jbc.M701448200.
Article CAS PubMed Google Scholar
Williams, C. C., Allison, J. G., Vidal, G. A., Burow, M. E., Beckman, B. S., Marrero, L., et al. (2004). The ERBB4/HER4 receptor tyrosine kinase regulates gene expression by functioning as a STAT5A nuclear chaperone. Journal of Cell Biology,167(3), 469–478. https://doi.org/10.1083/jcb.200403155.
Article CAS PubMed Google Scholar
Wolfe, M. S. (2019). Dysfunctional gamma-secretase in familial Alzheimer’s disease. Neurochemical Research,44(1), 5–11. https://doi.org/10.1007/s11064-018-2511-1.
Article CAS PubMed Google Scholar
Wong, H. K., Sakurai, T., Oyama, F., Kaneko, K., Wada, K., Miyazaki, H., et al. (2005). beta Subunits of voltage-gated sodium channels are novel substrates of beta-site amyloid precursor protein-cleaving enzyme (BACE1) and gamma-secretase. Journal of Biological Chemistry,280(24), 23009–23017. https://doi.org/10.1074/jbc.M414648200.
Article CAS PubMed Google Scholar
Wu, L., Walas, S. J., Leung, W., Lo, E. H., & Lok, J. (2015). Brain neurotrauma: Molecular, neuropsychological, and rehabilitation aspects. Boca Raton, FL: CRC Press.
Google Scholar
Wu, Q., Zhang, T., Cheng, J. F., Kim, Y., Grimwood, J., Schmutz, J., et al. (2001). Comparative DNA sequence analysis of mouse and human protocadherin gene clusters. Genome Research,11(3), 389–404. https://doi.org/10.1101/gr.167301.
Article CAS PubMed PubMed Central Google Scholar
Xu, J., Litterst, C., Georgakopoulos, A., Zaganas, I., & Robakis, N. K. (2009). Peptide EphB2/CTF2 generated by the gamma-secretase processing of EphB2 receptor promotes tyrosine phosphorylation and cell surface localization of N-methyl-D-aspartate receptors. Journal of Biological Chemistry,284(40), 27220–27228. https://doi.org/10.1074/jbc.M109.048728.
Article CAS PubMed Google Scholar
Yang, Z., Li, P. F., Chen, R. C., Wang, J., Wang, S., Shen, Y., et al. (2017). ADAM10-initiated release of notch intracellular domain regulates microtubule stability and radial migration of cortical neurons. Cerebral Cortex,27(2), 919–932. https://doi.org/10.1093/cercor/bhx006.
Article PubMed Google Scholar
Ying, Z., Misra, V., & Verge, V. M. (2014). Sensing nerve injury at the axonal ER: Activated Luman/CREB3 serves as a novel axonally synthesized retrograde regeneration signal. Proceedings of the National Academy of Sciences USA,111(45), 16142–16147. https://doi.org/10.1073/pnas.1407462111.
Article CAS Google Scholar
Yuk, D. Y., Lee, Y. K., Nam, S. Y., Yun, Y. W., Hwang, D. Y., Choi, D. Y., et al. (2009). Reduced anxiety in the mice expressing mutant (N141I) presenilin 2. Journal of Neuroscience Research,87(2), 522–531. https://doi.org/10.1002/jnr.21861.
Article CAS PubMed Google Scholar
Zatti, G., Burgo, A., Giacomello, M., Barbiero, L., Ghidoni, R., Sinigaglia, G., et al. (2006). Presenilin mutations linked to familial Alzheimer’s disease reduce endoplasmic reticulum and Golgi apparatus calcium levels. Cell Calcium,39(6), 539–550. https://doi.org/10.1016/j.ceca.2006.03.002.
Article CAS PubMed Google Scholar
Zhai, S., Ark, E. D., Parra-Bueno, P., & Yasuda, R. (2013). Long-distance integration of nuclear ERK signaling triggered by activation of a few dendritic spines. Science,342(6162), 1107–1111. https://doi.org/10.1126/science.1245622.
Article CAS PubMed PubMed Central Google Scholar
Zhang, C., Wu, B., Beglopoulos, V., Wines-Samuelson, M., Zhang, D., Dragatsis, I., et al. (2009). Presenilins are essential for regulating neurotransmitter release. Nature,460(7255), 632–636. https://doi.org/10.1038/nature08177.
Article CAS PubMed PubMed Central Google Scholar
Zhang, J., Yin, J. C., & Wesley, C. S. (2013). From Drosophila development to adult: Clues to Notch function in long-term memory. Front Cell Neurosci,7, 222. https://doi.org/10.3389/fncel.2013.00222.
Article CAS PubMed PubMed Central Google Scholar
Zhang, J., Yin, J. C., & Wesley, C. S. (2015). Notch intracellular domain (NICD) suppresses long-term memory formation in adult drosophila flies. Cellular and Molecular Neurobiology,35(6), 763–768. https://doi.org/10.1007/s10571-015-0183-9.
Article CAS PubMed PubMed Central Google Scholar
Zhang, D., Zhang, C., Ho, A., Kirkwood, A., Sudhof, T. C., & Shen, J. (2010). Inactivation of presenilins causes pre-synaptic impairment prior to post-synaptic dysfunction. Journal of Neurochemistry,115(5), 1215–1221. https://doi.org/10.1111/j.1471-4159.2010.07011.x.
Article CAS PubMed PubMed Central Google Scholar
Zhu, J. M., Li, K. X., Cao, S. X., Chen, X. J., Shen, C. J., Zhang, Y., et al. (2017). Increased NRG1-ErbB4 signaling in human symptomatic epilepsy. Science Reports,7(1), 141. https://doi.org/10.1038/s41598-017-00207-7.
Article CAS Google Scholar

Download references

Funding

Toh Hean Ch’ng was supported by Lee Kong Chian School of Medicine, Nanyang Technological University under Nanyang Assistant Professorship and Ministry of Education-Singapore under Grant Academic Research Fund Tier 1 (2016-T1-001-116).

Author information

Authors and Affiliations

Lee Kong Chian School of Medicine, Nanyang Technological University, Clinical Science Building, 11 Mandalay Road, 10-01-01 M, Singapore, 308232, Singapore
Yan Jun Lee & Toh Hean Ch’ng
School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
Toh Hean Ch’ng
Interdisciplinary Graduate School (IGS), Nanyang Technological University, Singapore, Singapore
Yan Jun Lee

Authors

Yan Jun Lee
View author publications
You can also search for this author in PubMed Google Scholar
Toh Hean Ch’ng
View author publications
You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Toh Hean Ch’ng.

Ethics declarations

Conflict of interest

The authors would like to declare that they have no conflicts of interest.

Informed Consent

Informed consent was obtained from all authors associated with the writing of this review article.

Research Involving Human and Animal Rights

This article does not contain any studies with human subjects or animals performed by any authors in the publication.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, Y.J., Ch’ng, T.H. RIP at the Synapse and the Role of Intracellular Domains in Neurons. Neuromol Med 22, 1–24 (2020). https://doi.org/10.1007/s12017-019-08556-4

Download citation

Received: 30 May 2019
Accepted: 12 July 2019
Published: 25 July 2019
Issue Date: March 2020
DOI: https://doi.org/10.1007/s12017-019-08556-4

Keywords

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

RIP at the Synapse and the Role of Intracellular Domains in Neurons

Abstract

Access this article

Similar content being viewed by others

Autophagy and the endolysosomal system in presynaptic function

The Role of Tomosyn in the Regulation of Neurotransmitter Release

The synaptic proteome

References

Funding

Author information

Authors and Affiliations

Corresponding author

Ethics declarations

Conflict of interest

Informed Consent

Research Involving Human and Animal Rights

Additional information

Publisher's Note

Rights and permissions

About this article

Cite this article

Keywords

Navigation

RIP at the Synapse and the Role of Intracellular Domains in Neurons

Abstract

Access this article

Similar content being viewed by others

Autophagy and the endolysosomal system in presynaptic function

The Role of Tomosyn in the Regulation of Neurotransmitter Release

The synaptic proteome

References

Funding

Author information

Authors and Affiliations

Corresponding author

Ethics declarations

Conflict of interest

Informed Consent

Research Involving Human and Animal Rights

Additional information

Publisher's Note

Rights and permissions

About this article

Cite this article

Share this article

Keywords

Search

Navigation