WNK1 is required during male pachynema to sustain fertility.
WNK1 is required during male pachynema to sustain fertility.
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DOI：
10.1016/j.isci.2023.107616
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发表时间：
2023-09-15
期刊：
影响因子：
5.8
通讯作者：
Demayo, Francesco
中科院分区：
文献类型：
--
作者：
Chi, Ru-pin Alicia;Xu, Xiaojiang;Li, Jian-Liang;Xu, Xin;Hu, Guang;Brown, Paula;Willson, Cynthia;Kirsanov, Oleksandr;Geyer, Christopher;Huang, Chou-Long;Morgan, Marcos;Demayo, Francesco
WNK 1是许多生理功能的重要调节因子，但其在雄性生殖中的作用尚未被探索。在雄性生殖系中，WNK 1在前细线期精母细胞中上调，表明在生精减数分裂中可能的功能。事实上，使用Wnt 7a-Cre小鼠在粗线期中期精母细胞中缺失Wnk 1导致男性不育，这类似于人类的非阻塞性无精子症，其中生殖细胞未能完成精子发生并且不产生精子。从机制上讲，我们发现在Wnk 1缺失的精母细胞中MTOR表达和信号传导升高。由于MTOR是翻译的中心介质，我们推测在这些精母细胞中翻译可能加速。支持这一点，我们发现顶体蛋白，ACRBP过早表达在精母细胞Wnk 1缺失。我们的研究揭示了男性生殖系中的MTOR调节因子，其对翻译具有潜在的影响，未来的研究将旨在了解WNK 1如何调节MTOR活性并在更广泛的范围内影响翻译。WNK 1激酶是精子发生不可或缺的WNK 1抑制精母细胞中的MTOR信号WNK 1的缺失与精母细胞中ACRBP的过早表达相关生理学;分子生物学;细胞生物学;组学;转录组学
WNK1 is an important regulator in many physiological functions, yet its role in male reproduction is unexplored. In the male germline, WNK1 is upregulated in preleptotene spermatocytes indicating possible function(s) in spermatogenic meiosis. Indeed, deletion of Wnk1 in mid-pachytene spermatocytes using the Wnt7a-Cre mouse led to male sterility which resembled non-obstructive azoospermia in humans, where germ cells failed to complete spermatogenesis and produced no sperm. Mechanistically, we found elevated MTOR expression and signaling in the Wnk1-depleted spermatocytes. As MTOR is a central mediator of translation, we speculated that translation may be accelerated in these spermatocytes. Supporting this, we found the acrosome protein, ACRBP to be prematurely expressed in the spermatocytes with Wnk1 deletion. Our study uncovered an MTOR-regulating factor in the male germline with potential implications in translation, and future studies will aim to understand how WNK1 regulates MTOR activity and impact translation on a broader spectrum. The kinase WNK1 is indispensable for spermatogenesis WNK1 represses MTOR signaling in the spermatocytes Loss of Wnk1 is associated with premature expression ACRBP in spermatocytes Physiology; Molecular biology; Cell biology; Omics; Transcriptomics
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影响因子：
14.9
作者：
Gene Ontology Consortium
通讯作者：
Gene Ontology Consortium
影响因子：
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作者：
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