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Pré-Publication, Document De Travail Année : 2021

Proteasome complexes experience profound structural and functional rearrangements throughout mammalian spermatogenesis

Charles Pineau

Résumé

Abstract 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 (>82-92%) 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.

Dates et versions

hal-03660083 , version 1 (22-10-2021)
hal-03660083 , version 2 (01-06-2023)

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Dušan Živković, Angelique Sanchez Dafun, Thomas Menneteau, Adrien Schahl, Sandrine Lise, et al.. Proteasome complexes experience profound structural and functional rearrangements throughout mammalian spermatogenesis. 2021. ⟨hal-03660083v1⟩
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