Sirt1 regulates acrosome biogenesis by modulating autophagic flux during spermiogenesis in mice
Sirt1 regulates acrosome biogenesis by modulating autophagic flux during spermiogenesis in mice
复制标题
Sirt1 通过调节小鼠精子发生过程中的自噬通量来调节顶体生物发生
DOI：
10.1242/dev.147074
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发表时间：
2017-02-01
期刊：
影响因子：
4.6
通讯作者：
Li, Wei
中科院分区：
文献类型：
--
作者：
Liu, Chao;Song, Zhenhua;Li, Wei
SIRT1是sirtuin蛋白家族的一员，在许多生物过程中起着重要的作用。SIRT1(-/-)小鼠表现出异常精子的频率增加，但Sirt1在精子发生中的机制仍然很大程度上仍不清楚。在这里，我们报告Sirt1可能直接参与生殖细胞的精子发生，而不是类固醇生成细胞。生殖细胞特异性Sirt1基因敲除小鼠几乎完全不育；Sirt1缺失后，精子发生中生殖细胞的早期有丝分裂和减数分裂进程没有受到明显影响，但随后的精子发生被顶体生物发生缺陷扰乱，导致了与人类球精症相似的表型。此外，精子细胞中Lc3和ATG7的脱乙酰基在Sirt1基因敲除后被破坏，从而影响Lc3从细胞核到细胞质的重新分配和自噬的激活。此外，Sirt1缺失导致LC3不能被招募到高尔基体衍生的小泡中，GOPC和PICK1也不能被招募到核相关的顶体小泡中。综上所述，这些发现揭示了Sirt1在顶体生物发生中具有新的生理功能。
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.