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

SYSNO ASEP	0559436
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Focal Adhesion Protein Vinculin Is Required for Proper Meiotic Progression during Mouse Spermatogenesis
Author(s)	Petrusová, Jana (UMG-J) Havalda, Robert (UMG-J) Flachs, Petr (UMG-J) Venit, Tomáš (UMG-J)_{RID, ORCID} Darášová, Alžběta (UMG-J) Hůlková, Lenka (UMG-J) Sztacho, Martin (UMG-J)_ORCID Hozák, Pavel (UMG-J)_{RID, ORCID}
Number of authors	8
Article number	2013
Source Title	Cells. - : MDPI Roč. 11, č. 13 (2022)
Number of pages	23 s.
Publication form	Online - E
Language	eng - English
Country	CH - Switzerland
Keywords	vinculin ; spermatogenesis ; centromere synapsis ; kinetochore ; ubiquitin-proteasome system ; fertility
Subject RIV	EB - Genetics ; Molecular Biology
OECD category	Cell biology
R&D Projects	GA19-05608S GA ČR - Czech Science Foundation (CSF)
	GA18-19714S GA ČR - Czech Science Foundation (CSF)
	LTC19048 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	LTC20024 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	EF16_013/0001775 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	EF18_046/0016045 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
Method of publishing	Open access
Institutional support	UMG-J - RVO:68378050
UT WOS	000825562500001
DOI	10.3390/cells11132013
Annotation	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.
Workplace	Institute of Molecular Genetics
Contact	Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217
Year of Publishing	2023
Electronic address	https://www.mdpi.com/2073-4409/11/13/2013

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