Membrane-Bound EMC10 Is Required for Sperm Motility via Maintaining the Homeostasis of Cytoplasm Sodium in Sperm.
Membrane-Bound EMC10 Is Required for Sperm Motility via Maintaining the Homeostasis of Cytoplasm Sodium in Sperm.
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膜结合的 EMC10 通过维持精子细胞质钠的稳态来维持精子活力
DOI：
10.3390/ijms231710069
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发表时间：
2022-09-03
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
内质网膜蛋白复合体10亚单位(EMC10)是一种进化上保守的跨物种多功能因子。我们以前报道过Emc10基因敲除(KO)导致小鼠不育。Emc10缺失的精子表现出多方面的功能障碍，包括精子活力降低。在Emc10 KO精子中，Na/K-ATPase的两个亚基ATP1A4和ATP1B3几乎缺失。在本研究中，在小鼠睾丸和附睾中发现了两种EMC10亚型：膜结合型(MEMC10)和分泌型(ScEMC10)亚型。我们提出的证据表明，通过正向调节生殖细胞中ATP1B3的表达，细胞质钠稳态所需要的是mEMC10，而不是scEMC10。睾丸内mEMC10过表达可挽救Emc10 KO引起的精子活力缺陷，而外源重组scEMC10蛋白不能提高Emc10 KO小鼠和弱精子症小鼠精子的活力。临床上，人类精子中ATP1B3和EMC10蛋白水平呈正相关，而精浆scEMC10蛋白水平与精子活力之间无相关性。这些结果突显了膜结合的EMC10亚型在维持细胞质钠稳态和精子运动方面的重要作用。根据目前的结果，mEMC10-Na，K/ATPaseα4β3轴被认为是一种新的调节细胞质钠和精子活力的机制，其成分似乎具有治疗弱精子症的潜力。
Endoplasmic reticulum membrane protein complex subunit 10 (EMC10) is an evolutionarily conserved and multifunctional factor across species. We previously reported that Emc10 knockout (KO) leads to mouse male infertility. Emc10-null spermatozoa exhibit multiple aspects of dysfunction, including reduced sperm motility. Two subunits of a Na/K-ATPase, ATP1A4 and ATP1B3, are nearly absent in Emc10 KO spermatozoa. Here, two isoforms of EMC10 were characterized in the mouse testis and epididymis: the membrane-bound (mEMC10) and secreted (scEMC10) isoforms. We present evidence that mEMC10, rather than scEMC10, is required for cytoplasm sodium homeostasis by positively regulating ATP1B3 expression in germ cells. Intra-testis mEMC10 overexpression rescued the sperm motility defect caused by Emc10 KO, while exogenous recombinant scEMC10 protein could not improve the motility of spermatozoa from either Emc10 KO mouse or asthenospermic subjects. Clinically, there is a positive association between ATP1B3 and EMC10 protein levels in human spermatozoa, whereas no correlation was proven between seminal plasma scEMC10 levels and sperm motility. These results highlight the important role of the membrane-bound EMC10 isoform in maintaining cytoplasm sodium homeostasis and sperm motility. Based on the present results, the mEMC10-Na, K/ATPase α4β3 axis is proposed as a novel mechanism underlying the regulation of cytoplasmic sodium and sperm motility, and its components seem to have therapeutic potential for asthenospermia.
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DOI：
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发表时间：
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影响因子：
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DOI：
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发表时间：
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影响因子：
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