USO1 Coordinates Centriolar Satellites to Regulate Male Germ Cell Proliferation and Cell Cycle Progression

TL;DR

This study shows that USO1 is crucial for male fertility by regulating germ cell proliferation and DNA repair.

Contribution

The novel contribution is identifying USO1's role in mammalian testis development and spermatogenesis.

Findings

USO1 depletion suppressed germ cell proliferation and induced apoptosis.

Uso1 knockout blocked cell cycle progression and impaired DNA damage repair.

USO1 is linked to centriolar satellites and regulates spermatogenesis-related genes.

Abstract

The endoplasmic reticulum–Golgi apparatus system is an important organelle regulating male reproduction. USO1 vesicle transport factor (USO1), as an important molecule in this system, is a general vesicular transport factor and regulates various biological processes in vivo. However, the potential role of USO1 in mammalian testis development and spermatogenesis has not been investigated. We documented the presence of USO1 in mouse germ cells and its functional roles by generating Uso1-knockout germ cell lines. Uso1 depletion suppressed cell proliferation and growth while stimulating apoptosis in GC1 and GC2 cells. In addition, the Uso1 knockout blocked cell cycle progression and weakened DNA damage repair. Mechanistically, USO1 is associated with male reproduction by regulating the expression of genes involved in spermatogenesis, and we found evidence that USO1 is closely linked to centriolar satellites (CSs), which may play an important biological role. Overall, our findings reveal a vital role for USO1 in male fertility and offer a significant understanding of the functions of golgin proteins in reproductive biology.

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