Abstract
Proteasomes are multisubunit complexes that degrade most intracellular proteins. Three of the 14 subunits of the 20S proteasome, specifically β1, β2, and β5, demonstrate catalytic activity and hydrolyze peptide bonds after acidic, basic, and hydrophobic amino acids, respectively. Within proteasome, the constitutive catalytic subunits β1, β2, and β5 can be substituted by the immune β1i, β2i, and β5i subunits, respectively. However, proteasomes do not always contain all the immune subunits at once; some proteasomes contain both immune and constitutive catalytic subunits simultaneously. Incorporation of immune subunits modifies the pattern of peptides produced by proteasomes. This is essential for antigen presentation and cellular response to stress as well as for a number of intracellular signaling pathways. We have developed a quantitative PCR-based system for the determination of the absolute levels of murine constitutive and immune proteasome subunits gene expression. Using the obtained system, we have estimated the expression levels of genes encoding proteasome subunits in the mouse central nervous system (CNS) tissues. We have shown that the quantity of transcripts of proteasome catalytic subunits in different CNS structures differed significantly. These data allow us to assume that the studied brain regions can be divided into two groups, with relatively “high” (cerebral cortex and spinal cord) and “low” (hippocampus and cerebellum) levels of proteasome subunit genes expression. Moreover, it was possible to distinguish structures with similar and significantly different gene expression profiles of proteasome catalytic subunits. Thus, the gene expression profiles in the cortex, spinal cord, and cerebellum were similar, but different from the expression profile in the hippocampus. Based on the obtained data, we suggest that there are differences in the proteasome pool, as well as in the functional load on the ubiquitin–proteasome system in different parts of the CNS.
Similar content being viewed by others
Notes
Abbreviations: CNS, central nervous system; UPS, ubiquitin-proteasome system.
REFERENCES
Groll M., Ditzel L., Löwe J., Stock D., Bochtler M., Bartunik H.D., Huber R. 1997. Structure of 20S proteasome from yeast at 2.4 A resolution. Nature. 386 (6624), 463–471.
Heinemeyer W., Fischer M., Krimmer T., Stachon U., Wolf D.H. 1997. The active sites of the eukaryotic 20 S proteasome and their involvement in subunit precursor processing. J. Biol. Chem. 272, 25200–25209.
Rousseau A., Bertolotti A. 2018. Regulation of proteasome assembly and activity in health and disease. Nat. Rev. Mol. Cell Biol. 19 (11), 697‒712.
Dantuma N.P., Bott L.C. 2014. The ubiquitin–proteasome system in neurodegenerative diseases: Precipitating factor, yet part of the solution. Front. Mol. Neurosci. 7, 70.
Morozov A.V., Karpov V.L. 2019. Proteasomes and several aspects of their heterogeneity relevant to cancer. Front. Oncol. 9, 761.
Kors S., Geijtenbeek K., Reits E., Schipper-Krom S. 2019. Regulation of proteasome activity by (post-)transcriptional mechanisms. Front. Mol. Biosci. 6, 48.
Pickering A.M., Koop A.L., Teoh C.Y., Ermak G., Grune T., Davies K.J. 2010. The immunoproteasome, the 20S proteasome and the PA28αβ proteasome regulator are oxidative-stress-adaptive proteolytic complexes. Biochem. J. 432, 585–594.
Ferrington D.A., Gregerson D.S. 2012. Immunoproteasomes: Structure, function, and antigen presentation. Prog. Mol. Biol. Transl. Sci. 109, 75–112.
Guillaume B., Chapiro J., Stroobant V., Colau D., Van Holle B., Parvizi G., Bousquet-Dubouch M.-P., Théate I., Parmentier N., Van den Eynde B. J. 2010. Two abundant proteasome subtypes that uniquely process some antigens presented by HLA class I molecules. Proc. Natl. Acad. Sci. U. S. A. 107, 18599–18604.
Morozov A.V., Karpov V.L. 2018. Biological consequences of structural and functional proteasome diversity. Heliyon. 4 (10), e00894.
Morozov A.V., Burov B.A., Astakhova T.M., Spasskaya D.S., Margulis B.A., Karpov V.L. 2019. Dynamics of the functional activity and expression of proteasome subunits during cellular adaptation to heat shock. Mol. Biol. (Moscow). 53 (4), 571‒579.
Kunjappu M.J., Hochstrasser M. 2014. Assembly of the 20S proteasome. Biochim. Biophys. Acta. 1843 (1), 2‒12.
Cembrowski M.S., Wang L., Sugino K., Shields B.C., Spruston N. 2016. Hipposeq: A comprehensive RNA-seq database of gene expression in hippocampal principal neurons. eLife. 5, e14997.
Funikov S.Y., Rezvykh A.P., Mazin P.V., Morozov A.V., Maltsev A.V., Chicheva M.M., Vikhareva E.A., Evgen’ev M.B., Ustyugov A.A. 2018. FUS(1‒359) transgenic mice as a model of ALS: pathophysiological and molecular aspects of the proteinopathy. Neurogenetics. 19 (3), 189‒204.
Liu Q., Huang S., Yin P., Yang S., Zhang J., Jing L., Cheng S., Tang B., Li X-J., Pan Y., Li S. 2020. Cerebellum-enriched protein INPP5A contributes to selective neuropathology in mouse model of spinocerebellar ataxias type 17. Nat. Commun. 11 (1), 1101.
Corriveau R.A., Huh G.S., Shatz C.J. 1998. Regulation of class I MHC gene expression in the developing and mature CNS by neural activity. Neuron. 21 (3), 505‒520.
McAllister A.K. 2014. Major histocompatibility complex I in brain development and schizophrenia. Biol. Psychiatry. 75 (4), 262–268.
Ramachandran K.V., Margolis S.S. 2017. A mammalian nervous-system-specific plasma membrane proteasome complex that modulates neuronal function. Nat. Struct. Mol. Biol. 24 (4), 419–430.
Ramachandran K.V., Fu J.M., Schaffer T.B., Na C.H., Delannoy M., Margolis S.S. 2018. Activity-dependent degradation of the nascentome by the neuronal membrane proteasome. Mol. Cell. 71 (1), 169–177.e6.
Orre M., Kamphuis W., Dooves S., Kooijman L., Chan E.T., Kirk C.J., Dimayuga Smith V., Koot S., Mamber C., Jansen A.H., Ovaa H., Hol E.M. 2013. Reactive glia show increased immunoproteasome activity in Alzheimer’s disease. Brain. 136 (5), 1415‒1431.
Frentzel S., Kuhn-Hartmann I., Gernold M., Gött P., Seelig A., Kloetzel P.M. 1993. The major-histocompatibility-complex-encoded beta-type proteasome subunits LMP2 and LMP7. Evidence that LMP2 and LMP7 are synthesized as proproteins and that cellular levels of both mRNA and LMP-containing 20S proteasomes are differentially regulated. Eur. J. Biochem. 216 (1), 119‒126.
Funding
This study was supported by the Russian Science Foundation, grant no. 18-74-10095. Animal housing was supported by the Program for Support of Bioresource Collections of the Institute of Physiologically Active Substances, Russian Academy of Sciences, Federal Agency of Scientific Organizations, project no. 0090-2017-0016.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest. The authors declare no conflict of interest.
Statement on the welfare of animals. The experiments were performed in accordance with the international, national, and/or institutional guidelines for the care and use of animals, and with the Order of the Ministry of Health Care of the Russian Federation no. 199n, April 1, 2016 “On approval of the rules of good laboratory practice.”
Additional information
Translated by M. Stepanichev
Rights and permissions
About this article
Cite this article
Funikov, S.Y., Spasskaya, D.S., Burov, A.V. et al. Structures of the Mouse Central Nervous System Contain Different Quantities of Proteasome Gene Transcripts. Mol Biol 55, 47–55 (2021). https://doi.org/10.1134/S0026893320060047
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S0026893320060047