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The dynamic nuclear periphery as a facilitator of gamete health and rejuvenation

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Abstract

The nuclear periphery is a hotspot for the accumulation of age-induced damage in eukaryotic cells. The types of damage that occur at the periphery and their phenotypic consequences have begun to be characterized; however, the mechanisms by which cells repair or eliminate nuclear damage remain poorly understood. Using budding yeast meiosis as a natural system to study cellular rejuvenation, we recently discovered a novel nuclear quality control event, in which age-induced damage is sequestered away from dividing chromosomes to a discarded nuclear compartment that we term the GUNC (for “Gametogenesis Uninherited Nuclear Compartment”). Interestingly, extensive nuclear remodeling occurs even in young cells, including a surprising modularity of the nuclear pore complex, suggesting a general contribution to gamete fitness. In this review, we discuss these findings in the context of recent evidence that the nuclear periphery is a highly dynamic region critical for cellular health.

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References

  • Arai K, Sato M, Tanaka K, Yamamoto M (2010) Nuclear compartmentalization is abolished during fission yeast meiosis. Curr Biol CB 20:1913–1918

    Article  CAS  PubMed  Google Scholar 

  • Asakawa H, Kojidani T, Mori C, Osakada H, Sato M, Ding DQ, Hiraoka Y, Haraguchi T (2010) Virtual breakdown of the nuclear envelope in fission yeast meiosis. Curr Biol CB 20:1919–1925

    Article  CAS  PubMed  Google Scholar 

  • Boettcher B, Barral Y (2013) The cell biology of open and closed mitosis. Nucleus (Austin, Tex) 4:160–165

    Google Scholar 

  • Boettcher B, Marquez-Lago TT, Bayer M, Weiss EL, Barral Y (2012) Nuclear envelope morphology constrains diffusion and promotes asymmetric protein segregation in closed mitosis. J Cell Biol 197:921–937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bohnert KA, Kenyon C (2017) A lysosomal switch triggers proteostasis renewal in the immortal C. elegans germ lineage. Nature 551:629–633

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bonev B, Cavalli G (2016) Organization and function of the 3D genome. Nat Rev Genet 17:772

    Article  CAS  PubMed  Google Scholar 

  • Buchwalter A, Hetzer MW (2017) Nucleolar expansion and elevated protein translation in premature aging. Nat Commun 8:328

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cabrera M, Novarina D, Rempel IL, Veenhoff LM, Chang M (2017) A simple microfluidic platform to study age-dependent protein abundance and localization changes in Saccharomyces cerevisiae. Microbial Cell (Graz, Austria) 4:169–174

    Article  CAS  Google Scholar 

  • Caudron F, Barral Y (2009) Septins and the lateral compartmentalization of eukaryotic membranes. Dev Cell 16:493–506

    Article  CAS  PubMed  Google Scholar 

  • Chao JT, Wong AK, Tavassoli S, Young BP, Chruscicki A, Fang NN, Howe LJ, Mayor T, Foster LJ, Loewen CJ (2014) Polarization of the endoplasmic reticulum by ER-septin tethering. Cell 158:620–632

    Article  CAS  PubMed  Google Scholar 

  • Chou CC, Zhang Y, Umoh ME, Vaughan SW, Lorenzini I, Liu F, Sayegh M, Donlin-Asp PG, Chen YH, Duong DM et al (2018) TDP-43 pathology disrupts nuclear pore complexes and nucleocytoplasmic transport in ALS/FTD. Nat Neurosci 21:228–239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chu DB, Gromova T, Newman TAC, Burgess SM (2017) The nucleoporin Nup2 contains a meiotic-autonomous region that promotes the dynamic chromosome events of meiosis. Genetics 206:1319–1337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clay L, Caudron F, Denoth-Lippuner A, Boettcher B, Buvelot Frei S, Snapp EL, Barral Y (2014) A sphingolipid-dependent diffusion barrier confines ER stress to the yeast mother cell. eLife 3:e01883

    Article  PubMed  PubMed Central  Google Scholar 

  • Colombi P, Webster BM, Frohlich F, Lusk CP (2013) The transmission of nuclear pore complexes to daughter cells requires a cytoplasmic pool of Nsp1. J Cell Biol 203:215–232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • D'Angelo MA, Raices M, Panowski SH, Hetzer MW (2009) Age-dependent deterioration of nuclear pore complexes causes a loss of nuclear integrity in postmitotic cells. Cell 136:284–295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De Souza CP, Osmani AH, Hashmi SB, Osmani SA (2004) Partial nuclear pore complex disassembly during closed mitosis in Aspergillus nidulans. Curr Biol CB 14:1973–1984

    Article  PubMed  CAS  Google Scholar 

  • Denning D, Mykytka B, Allen NP, Huang L, Al B, Rexach M (2001) The nucleoporin Nup60p functions as a Gsp1p-GTP-sensitive tether for Nup2p at the nuclear pore complex. J Cell Biol 154:937–950

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Denoth-Lippuner A, Krzyzanowski MK, Stober C, Barral Y (2014) Role of SAGA in the asymmetric segregation of DNA circles during yeast ageing. eLife 3:e03790

    Article  PubMed Central  Google Scholar 

  • Dilworth DJ, Suprapto A, Padovan JC, Chait BT, Wozniak RW, Rout MP, Aitchison JD (2001) Nup2p dynamically associates with the distal regions of the yeast nuclear pore complex. J Cell Biol 153:1465–1478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dultz E, Zanin E, Wurzenberger C, Braun M, Rabut G, Sironi L, Ellenberg J (2008) Systematic kinetic analysis of mitotic dis- and reassembly of the nuclear pore in living cells. J Cell Biol 180:857–865

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eastwood MD, Meneghini MD (2015) Developmental coordination of gamete differentiation with programmed cell death in sporulating yeast. Eukaryot Cell 14:858–867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eastwood MD, Cheung SW, Lee KY, Moffat J, Meneghini MD (2012) Developmentally programmed nuclear destruction during yeast gametogenesis. Dev Cell 23:35–44

    Article  CAS  PubMed  Google Scholar 

  • Eriksson M, Brown WT, Gordon LB, Glynn MW, Singer J, Scott L, Erdos MR, Robbins CM, Moses TY, Berglund P et al (2003) Recurrent de novo point mutations in lamin A cause Hutchinson–Gilford progeria syndrome. Nature 423:293–298

    Article  CAS  PubMed  Google Scholar 

  • Fawcett DW, Chemes HE (1979) Changes in distribution of nuclear pores during differentiation of the male germ cells. Tissue Cell 11:147–162

    Article  CAS  PubMed  Google Scholar 

  • Flor-Parra I, Iglesias-Romero AB, Salas-Pino S, Lucena R, Jimenez J, Daga RR (2018) Importin alpha and vNEBD control meiotic spindle disassembly in fission yeast. Cell Rep 23:933–941

    Article  CAS  PubMed  Google Scholar 

  • Folz, H., Nino, C.A., Taranum, S., Caesar, S., Latta, L., Waharte, F., Salamero, J., Schlenstedt, G., and Dargemont, C. (2019). SUMOylation of the nuclear pore complex basket is involved in sensing cellular stresses. J Cell Sci 132, jcs224279.

  • Galy V, Gadal O, Fromont-Racine M, Romano A, Jacquier A, Nehrbass U (2004) Nuclear retention of unspliced mRNAs in yeast is mediated by perinuclear Mlp1. Cell 116:63–73

    Article  CAS  PubMed  Google Scholar 

  • Gasset-Rosa F, Chillon-Marinas C, Goginashvili A, Atwal RS, Artates JW, Tabet R, Wheeler VC, Bang AG, Cleveland DW, Lagier-Tourenne C (2017) Polyglutamine-expanded huntingtin exacerbates age-related disruption of nuclear integrity and nucleocytoplasmic transport. Neuron 94:48–57.e44

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gehlen LR, Nagai S, Shimada K, Meister P, Taddei A, Gasser SM (2011) Nuclear geometry and rapid mitosis ensure asymmetric episome segregation in yeast. Curr Biol CB 21:25–33

    Article  CAS  PubMed  Google Scholar 

  • Goudeau J, Aguilaniu H (2010) Carbonylated proteins are eliminated during reproduction in C. elegans. Aging Cell 9:991–1003

    Article  CAS  PubMed  Google Scholar 

  • Grima JC, Daigle JG, Arbez N, Cunningham KC, Zhang K, Ochaba J, Geater C, Morozko E, Stocksdale J, Glatzer JC et al (2017) Mutant Huntingtin disrupts the nuclear pore complex. Neuron 94:93–107.e106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ho HC (2010) Redistribution of nuclear pores during formation of the redundant nuclear envelope in mouse spermatids. J Anat 216:525–532

    Article  PubMed  PubMed Central  Google Scholar 

  • Khmelinskii A, Blaszczak E, Pantazopoulou M, Fischer B, Omnus DJ, Le Dez G, Brossard A, Gunnarsson A, Barry JD, Meurer M et al (2014) Protein quality control at the inner nuclear membrane. Nature 516:410–413

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • King GA, Goodman JS, Schick JG, Chetlapalli K, Jorgens DM, McDonald KL, Ünal E (2019) Meiotic cellular rejuvenation is coupled to nuclear remodeling in budding yeast. eLife 8:e47156

    Article  PubMed  PubMed Central  Google Scholar 

  • Laurell E, Beck K, Krupina K, Theerthagiri G, Bodenmiller B, Horvath P, Aebersold R, Antonin W, Kutay U (2011) Phosphorylation of Nup98 by multiple kinases is crucial for NPC disassembly during mitotic entry. Cell 144:539–550

    Article  CAS  PubMed  Google Scholar 

  • Lord CL, Timney BL, Rout MP, Wente SR (2015) Altering nuclear pore complex function impacts longevity and mitochondrial function in S. cerevisiae. J Cell Biol 208:729–744

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Makio T, Lapetina DL, Wozniak RW (2013) Inheritance of yeast nuclear pore complexes requires the Nsp1p subcomplex. J Cell Biol 203:187–196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Markossian S, Suresh S, Osmani AH, Osmani SA (2015) Nup2 requires a highly divergent partner, NupA, to fulfill functions at nuclear pore complexes and the mitotic chromatin region. Mol Biol Cell 26:605–621

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Meszaros N, Cibulka J, Mendiburo MJ, Romanauska A, Schneider M, Kohler A (2015) Nuclear pore basket proteins are tethered to the nuclear envelope and can regulate membrane curvature. Dev Cell 33:285–298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller SB, Ho CT, Winkler J, Khokhrina M, Neuner A, Mohamed MY, Guilbride DL, Richter K, Lisby M, Schiebel E et al (2015) Compartment-specific aggregases direct distinct nuclear and cytoplasmic aggregate deposition. The EMBO journal 34:778–797

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mochida K, Oikawa Y, Kimura Y, Kirisako H, Hirano H, Ohsumi Y, Nakatogawa H (2015) Receptor-mediated selective autophagy degrades the endoplasmic reticulum and the nucleus. Nature 522:359–362

    Article  CAS  PubMed  Google Scholar 

  • Moens PB (1971) Fine structure of ascospore development in the yeast Saccharomyces cerevisiae. Can J Microbiol 17:507–510

    Article  CAS  PubMed  Google Scholar 

  • Moens PB, Rapport E (1971) Spindles, spindle plaques, and meiosis in the yeast Saccharomyces cerevisiae (Hansen). J Cell Biol 50:344–361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morlot S, Song J, Leger-Silvestre I, Matifas A, Gadal O, Charvin G (2019) Excessive rDNA transcription drives the disruption in nuclear homeostasis during entry into senescence in budding yeast. Cell Rep 28:408–422.e404

    Article  CAS  PubMed  Google Scholar 

  • Niepel M, Molloy KR, Williams R, Farr JC, Meinema AC, Vecchietti N, Cristea IM, Chait BT, Rout MP, Strambio-De-Castillia C (2013) The nuclear basket proteins Mlp1p and Mlp2p are part of a dynamic interactome including Esc1p and the proteasome. Mol Biol Cell 24:3920–3938

    Article  PubMed  PubMed Central  Google Scholar 

  • Nino CA, Guet D, Gay A, Brutus S, Jourquin F, Mendiratta S, Salamero J, Geli V, Dargemont C (2016) Posttranslational marks control architectural and functional plasticity of the nuclear pore complex basket. J Cell Biol 212:167–180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Otsuka S, Bui KH, Schorb M, Hossain MJ, Politi AZ, Koch B, Eltsov M, Beck M, Ellenberg J (2016) Nuclear pore assembly proceeds by an inside-out extrusion of the nuclear envelope. eLife 5:e19071

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rabut G, Doye V, Ellenberg J (2004) Mapping the dynamic organization of the nuclear pore complex inside single living cells. Nat Cell Biol 6:1114–1121

    Article  CAS  PubMed  Google Scholar 

  • Raices M, D'Angelo MA (2012) Nuclear pore complex composition: a new regulator of tissue-specific and developmental functions. Nat Rev Mol Cell Biol 13:687–699

    Article  CAS  PubMed  Google Scholar 

  • Rempel IL, Crane MM, Thaller DJ, Mishra A, Jansen DP, Janssens G, Popken P, Aksit A, Kaeberlein M, van der Giessen E et al (2019) Age-dependent deterioration of nuclear pore assembly in mitotic cells decreases transport dynamics. eLife 8:e48186

    Article  PubMed  PubMed Central  Google Scholar 

  • Romanauska A, Kohler A (2018) The inner nuclear membrane is a metabolically active territory that generates nuclear lipid droplets. Cell 174:700–715.e718

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saarikangas J, Barral Y (2011) The emerging functions of septins in metazoans. EMBO Rep 12:1118–1126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saarikangas J, Caudron F, Prasad R, Moreno DF, Bolognesi A, Aldea M, Barral Y (2017) Compartmentalization of ER-bound chaperone confines protein deposit formation to the aging yeast cell. Curr Biol CB 27:773–783

    Article  CAS  PubMed  Google Scholar 

  • Savas JN, Toyama BH, Xu T, Yates JR 3rd, Hetzer MW (2012) Extremely long-lived nuclear pore proteins in the rat brain. Science (New York, NY) 335:942

    Article  CAS  Google Scholar 

  • Sinclair DA, Guarente L (1997) Extrachromosomal rDNA circles—a cause of aging in yeast. Cell 91:1033–1042

    Article  CAS  PubMed  Google Scholar 

  • Sinclair DA, Mills K, Guarente L (1997) Accelerated aging and nucleolar fragmentation in yeast sgs1 mutants. Science (New York, NY) 277:1313–1316

    Article  CAS  Google Scholar 

  • Singh P, Li R (2018) Emerging roles for sphingolipids in cellular aging. Curr Genet 64:761–767

    Article  CAS  PubMed  Google Scholar 

  • Smoyer CJ, Jaspersen SL (2019) Patrolling the nucleus: inner nuclear membrane-associated degradation. Curr Genet 65:1099–1106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smoyer CJ, Smith SE, Gardner JM, McCroskey S, Unruh JR, Jaspersen SL (2019) Distribution of proteins at the inner nuclear membrane is regulated by the Asi1 E3 ligase in Saccharomyces cerevisiae. Genetics 211:1269–1282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Suresh S, Markossian S, Osmani AH, Osmani SA (2017) Mitotic nuclear pore complex segregation involves Nup2 in Aspergillus nidulans. J Cell Biol 216:2813–2826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tiku V, Jain C, Raz Y, Nakamura S, Heestand B, Liu W, Spath M, Suchiman HED, Muller RU, Slagboom PE et al (2017) Small nucleoli are a cellular hallmark of longevity. Nat Commun 8:16083

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Toyama BH, Savas JN, Park SK, Harris MS, Ingolia NT, Yates JR 3rd, Hetzer MW (2013) Identification of long-lived proteins reveals exceptional stability of essential cellular structures. Cell 154:971–982

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Toyama BH, Arrojo EDR, Lev-Ram V, Ramachandra R, Deerinck TJ, Lechene C, Ellisman MH, Hetzer MW (2019) Visualization of long-lived proteins reveals age mosaicism within nuclei of postmitotic cells. J Cell Biol 218:433–444

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Troyer D, Schwager P (1982) Evidence for nuclear membrane fluidity: Proacrosome migration and nuclear pore redistribution during grasshopper spermiogenesis. Cell Motil 2:355–367

    Article  Google Scholar 

  • Ünal E, Amon A (2011) Gamete formation resets the aging clock in yeast. Cold Spring Harb Symp Quant Biol 76:73–80

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ünal E, Kinde B, Amon A (2011) Gametogenesis eliminates age-induced cellular damage and resets life span in yeast. Science (New York, NY) 332:1554–1557

    Article  CAS  Google Scholar 

  • Ungricht R, Kutay U (2017) Mechanisms and functions of nuclear envelope remodelling. Nat Rev Mol Cell Biol 18:229–245

    Article  CAS  PubMed  Google Scholar 

  • Van de Vosse DW, Wan Y, Wozniak RW, Aitchison JD (2011) Role of the nuclear envelope in genome organization and gene expression. Wiley Interdiscip Rev Syst Biol Med 3:147–166

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Walters AD, May CK, Dauster ES, Cinquin BP, Smith EA, Robellet X, D'Amours D, Larabell CA, Cohen-Fix O (2014) The yeast polo kinase Cdc5 regulates the shape of the mitotic nucleus. Curr Biol CB 24:2861–2867

    Article  CAS  PubMed  Google Scholar 

  • Webster BM, Colombi P, Jager J, Lusk CP (2014) Surveillance of nuclear pore complex assembly by ESCRT-III/Vps4. Cell 159:388–401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Witkin KL, Chong Y, Shao S, Webster MT, Lahiri S, Walters AD, Lee B, Koh JL, Prinz WA, Andrews BJ et al (2012) The budding yeast nuclear envelope adjacent to the nucleolus serves as a membrane sink during mitotic delay. Curr Biol CB 22:1128–1133

    Article  CAS  PubMed  Google Scholar 

  • Zhang K, Donnelly CJ, Haeusler AR, Grima JC, Machamer JB, Steinwald P, Daley EL, Miller SJ, Cunningham KM, Vidensky S et al (2015) The C9orf72 repeat expansion disrupts nucleocytoplasmic transport. Nature 525:56–61

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We would like to thank Jay Goodman and Tina Sing for their helpful discussions regarding this manuscript. GAK is supported by a National Science Foundation Graduate Research Fellowship (DGE 1752814) and a National Institutes of Health Traineeship (T32 GM007232). EÜ is supported by funds from the Pew Charitable Trusts (00027344), Damon Runyon Cancer Research Foundation (35-15), National Institutes of Health (DP2 AG055946-01), Shurl and Kay Curci Foundation, and Glenn Foundation for Medical Research.

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  1. Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, 94720, USA

    Grant A. King & Elçin Ünal

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King, G.A., Ünal, E. The dynamic nuclear periphery as a facilitator of gamete health and rejuvenation. Curr Genet 66, 487–493 (2020). https://doi.org/10.1007/s00294-019-01050-1

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