MFN2 interacts with nuage-associated proteins and is essential for male germ cell development by controlling mRNA fate during spermatogenesis

被引：13

作者：

Wang, Xiaoli ^{[1
]}

Wen, Yujiao ^{[1
]}

Zhang, Jin ^{[1
]}

Swanson, Grace ^{[2
]}

Guo, Shuangshuang ^{[1
]}

Cao, Congcong ^{[1
]}

Krawetz, Stephen A. ^{[2
]}

Zhang, Zhibing ^{[2
,3
]}

Yuan, Shuiqiao ^{[1
,4
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Inst Reprod Hlth, Wuhan 430030, Hubei, Peoples R China

[2] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA

[3] Wayne State Univ, Dept Physiol, Detroit, MI 48201 USA

[4] Shenzhen Huazhong Univ Sci & Technol, Res Inst, Shenzhen 518057, Guangdong, Peoples R China

来源：

DEVELOPMENT | 2021年 / 148卷 / 07期

基金：

中国国家自然科学基金;

关键词：

Nuage proteins; Mitofusins; MSY2; Spermatogenesis; Mice; MITOCHONDRIAL FUSION; ENDOPLASMIC-RETICULUM; GENE-EXPRESSION; MITOFUSIN; CHROMATOID BODY; MOUSE; MSY2; IDENTIFICATION; TRANSLATION; TRANSCRIPTS;

D O I：

10.1242/dev.196295

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Mitochondria play a crucial role in spermatogenesis and are regulated by several mitochondrial fusion proteins. However, their functional importance associated with their structure formation and mRNA fate regulation during spermatogenesis remains unclear. Here, we show that mitofusin 2 (MFN2), a mitochondrial fusion protein, interacts with nuage associated proteins (including MIWI, DDX4, TDRKH and GASZ) in mice. Conditional mutation of Mfn2 in postnatal germ cells results in male sterility due to germ cell developmental defects. Moreover, MFN2 interacts with MFN1, another mitochondrial fusion protein with a high sequence similarity to MFN2, in testes to facilitate spermatogenesis. Simultaneous mutation of Mfn1 and Mfn2 in testes causes very severe infertile phenotypes. Importantly, we show that MFN2 is enriched in polysome fractions of testes and interacts with MSY2, a germ cell specific DNA/RNA-binding protein, to control gamete-specific mRNA (such as Spata19) translational activity during spermatogenesis. Collectively, our findings demonstrate that MFN2 interacts with nuage associated proteins and MSY2 to regulate male germ cell development by controlling several gamete-specific mRNA fates.

引用

页数：14