Sirt1 regulates acrosome biogenesis by modulating autophagic flux during spermiogenesis in mice.

Sirt1 is a member of the sirtuin family of proteins and has important roles in numerous biological processes. Sirt1-/- mice display an increased frequency of abnormal spermatozoa, but the mechanism of Sirt1 in spermiogenesis remains largely unknown. Here, we report that Sirt1 might be directly involved in spermiogenesis in germ cells but not in steroidogenic cells. Germ cell-specific Sirt1 knockout mice were almost completely infertile; the early mitotic and meiotic progression of germ cells in spermatogenesis were not obviously affected after Sirt1 depletion, but subsequent spermiogenesis was disrupted by a defect in acrosome biogenesis, which resulted in a phenotype similar to that observed in human globozoospermia. In addition, LC3 and Atg7 deacetylation was disrupted in spermatids after knocking out Sirt1, which affected the redistribution of LC3 from the nucleus to the cytoplasm and the activation of autophagy. Furthermore, Sirt1 depletion resulted in the failure of LC3 to be recruited to Golgi apparatus-derived vesicles and in the failure of GOPC and PICK1 to be recruited to nucleus-associated acrosomal vesicles. Taken together, these findings reveal that Sirt1 has a novel physiological function in acrosome biogenesis. © 2017. Published by The Company of Biologists Ltd.

Citation

Chao Liu, Zhenhua Song, Lina Wang, Haiyan Yu, Weixiao Liu, Yongliang Shang, Zhiliang Xu, Haichao Zhao, Fengyi Gao, Jiamin Wen, Linan Zhao, Yaoting Gui, Jianwei Jiao, Fei Gao, Wei Li. Sirt1 regulates acrosome biogenesis by modulating autophagic flux during spermiogenesis in mice. Development (Cambridge, England). 2017 Feb 01;144(3):441-451

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PMID: 28003215

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