Focal Adhesion Protein Vinculin Is Required for Proper Meiotic Progression during Mouse Spermatogenesis

0559436 - ÚMG 2023 RIV CH eng J - Článek v odborném periodiku
Petrusová, Jana - Havalda, Robert - Flachs, Petr - Venit, Tomáš - Darášová, Alžběta - Hůlková, Lenka - Sztacho, Martin - Hozák, Pavel
Focal Adhesion Protein Vinculin Is Required for Proper Meiotic Progression during Mouse Spermatogenesis.
Cells. Roč. 11, č. 13 (2022), č. článku 2013. E-ISSN 2073-4409
Grant CEP: GA ČR GA19-05608S; GA ČR(CZ) GA18-19714S; GA MŠMT LTC19048; GA MŠMT LTC20024; GA MŠMT(CZ) ED1.1.00/02.0109; GA MŠMT(CZ) EF16_013/0001775; GA MŠMT(CZ) EF18_046/0016045
Grant ostatní: AV ČR(CZ) JSPS-20-06
Program: Bilaterální spolupráce
Institucionální podpora: RVO:68378050
Klíčová slova: vinculin * spermatogenesis * centromere synapsis * kinetochore * ubiquitin-proteasome system * fertility
Obor OECD: Cell biology
Impakt faktor: 6, rok: 2022
Způsob publikování: Open access
https://www.mdpi.com/2073-4409/11/13/2013

The focal adhesion protein Vinculin (VCL) is ascribed to various cytoplasmic functions, however, its nuclear role has so far been ambiguous. We observed that VCL localizes to the nuclei of mouse primary spermatocytes undergoing first meiotic division. Specifically, VCL localizes along the meiosis-specific structure synaptonemal complex (SC) during prophase I and the centromeric regions, where it remains until metaphase I. To study the role of VCL in meiotic division, we prepared a conditional knock-out mouse (VCLcKO). We found that the VCLcKO male mice were semi-fertile, with a decreased number of offspring compared to wild-type animals. This study of events in late prophase I indicated premature splitting of homologous chromosomes, accompanied by an untimely loss of SCP1. This caused erroneous kinetochore formation, followed by failure of the meiotic spindle assembly and metaphase I arrest. To assess the mechanism of VCL involvement in meiosis, we searched for its possible interacting partners. A mass spectrometry approach identified several putative interactors which belong to the ubiquitin-proteasome pathway (UPS). The depletion of VLC leads to the dysregulation of a key subunit of the proteasome complex in the meiotic nuclei and an altered nuclear SUMOylation level. Taken together, we show for the first time the presence of VCL in the nucleus of spermatocytes and its involvement in proper meiotic progress. It also suggests the direction for future studies regarding the role of VCL in spermatogenesis through regulation of UPS.
Trvalý link: https://hdl.handle.net/11104/0332876