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Proteasome complexes experience profound structural and functional rearrangements throughout mammalian spermatogenesis
During spermatogenesis, spermatogonia undergo a series of mitotic and meiotic divisions on their path to spermatozoa. To achieve this, a succession of processes requiring high proteolytic activity are in part orchestrated by the proteasome. The spermatoproteasome (s20S) is specific to the developing...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9169623/ https://www.ncbi.nlm.nih.gov/pubmed/35377789 http://dx.doi.org/10.1073/pnas.2116826119 |
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author | Živković, Dušan Sanchez Dafun, Angelique Menneteau, Thomas Schahl, Adrien Lise, Sandrine Kervarrec, Christine Toste Rêgo, Ana da Fonseca, Paula C. A. Chavent, Matthieu Pineau, Charles Burlet-Schiltz, Odile Marcoux, Julien Bousquet, Marie-Pierre |
author_facet | Živković, Dušan Sanchez Dafun, Angelique Menneteau, Thomas Schahl, Adrien Lise, Sandrine Kervarrec, Christine Toste Rêgo, Ana da Fonseca, Paula C. A. Chavent, Matthieu Pineau, Charles Burlet-Schiltz, Odile Marcoux, Julien Bousquet, Marie-Pierre |
author_sort | Živković, Dušan |
collection | PubMed |
description | During spermatogenesis, spermatogonia undergo a series of mitotic and meiotic divisions on their path to spermatozoa. To achieve this, a succession of processes requiring high proteolytic activity are in part orchestrated by the proteasome. The spermatoproteasome (s20S) is specific to the developing gametes, in which the gamete-specific α4s subunit replaces the α4 isoform found in the constitutive proteasome (c20S). Although the s20S is conserved across species and was shown to be crucial for germ cell development, its mechanism, function, and structure remain incompletely characterized. Here, we used advanced mass spectrometry (MS) methods to map the composition of proteasome complexes and their interactomes throughout spermatogenesis. We observed that the s20S becomes highly activated as germ cells enter meiosis, mainly through a particularly extensive 19S activation and, to a lesser extent, PA200 binding. Additionally, the proteasome population shifts from c20S (98%) to s20S (>82 to 92%) during differentiation, presumably due to the shift from α4 to α4s expression. We demonstrated that s20S, but not c20S, interacts with components of the meiotic synaptonemal complex, where it may localize via association with the PI31 adaptor protein. In vitro, s20S preferentially binds to 19S and displays higher trypsin- and chymotrypsin-like activities, both with and without PA200 activation. Moreover, using MS methods to monitor protein dynamics, we identified significant differences in domain flexibility between α4 and α4s. We propose that these differences induced by α4s incorporation result in significant changes in the way the s20S interacts with its partners and dictate its role in germ cell differentiation. |
format | Online Article Text |
id | pubmed-9169623 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-91696232022-10-04 Proteasome complexes experience profound structural and functional rearrangements throughout mammalian spermatogenesis Živković, Dušan Sanchez Dafun, Angelique Menneteau, Thomas Schahl, Adrien Lise, Sandrine Kervarrec, Christine Toste Rêgo, Ana da Fonseca, Paula C. A. Chavent, Matthieu Pineau, Charles Burlet-Schiltz, Odile Marcoux, Julien Bousquet, Marie-Pierre Proc Natl Acad Sci U S A Biological Sciences During spermatogenesis, spermatogonia undergo a series of mitotic and meiotic divisions on their path to spermatozoa. To achieve this, a succession of processes requiring high proteolytic activity are in part orchestrated by the proteasome. The spermatoproteasome (s20S) is specific to the developing gametes, in which the gamete-specific α4s subunit replaces the α4 isoform found in the constitutive proteasome (c20S). Although the s20S is conserved across species and was shown to be crucial for germ cell development, its mechanism, function, and structure remain incompletely characterized. Here, we used advanced mass spectrometry (MS) methods to map the composition of proteasome complexes and their interactomes throughout spermatogenesis. We observed that the s20S becomes highly activated as germ cells enter meiosis, mainly through a particularly extensive 19S activation and, to a lesser extent, PA200 binding. Additionally, the proteasome population shifts from c20S (98%) to s20S (>82 to 92%) during differentiation, presumably due to the shift from α4 to α4s expression. We demonstrated that s20S, but not c20S, interacts with components of the meiotic synaptonemal complex, where it may localize via association with the PI31 adaptor protein. In vitro, s20S preferentially binds to 19S and displays higher trypsin- and chymotrypsin-like activities, both with and without PA200 activation. Moreover, using MS methods to monitor protein dynamics, we identified significant differences in domain flexibility between α4 and α4s. We propose that these differences induced by α4s incorporation result in significant changes in the way the s20S interacts with its partners and dictate its role in germ cell differentiation. National Academy of Sciences 2022-04-04 2022-04-12 /pmc/articles/PMC9169623/ /pubmed/35377789 http://dx.doi.org/10.1073/pnas.2116826119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Živković, Dušan Sanchez Dafun, Angelique Menneteau, Thomas Schahl, Adrien Lise, Sandrine Kervarrec, Christine Toste Rêgo, Ana da Fonseca, Paula C. A. Chavent, Matthieu Pineau, Charles Burlet-Schiltz, Odile Marcoux, Julien Bousquet, Marie-Pierre Proteasome complexes experience profound structural and functional rearrangements throughout mammalian spermatogenesis |
title | Proteasome complexes experience profound structural and functional rearrangements throughout mammalian spermatogenesis |
title_full | Proteasome complexes experience profound structural and functional rearrangements throughout mammalian spermatogenesis |
title_fullStr | Proteasome complexes experience profound structural and functional rearrangements throughout mammalian spermatogenesis |
title_full_unstemmed | Proteasome complexes experience profound structural and functional rearrangements throughout mammalian spermatogenesis |
title_short | Proteasome complexes experience profound structural and functional rearrangements throughout mammalian spermatogenesis |
title_sort | proteasome complexes experience profound structural and functional rearrangements throughout mammalian spermatogenesis |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9169623/ https://www.ncbi.nlm.nih.gov/pubmed/35377789 http://dx.doi.org/10.1073/pnas.2116826119 |
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