The Na+ and K+ transport system of sperm (ATP1A4) is essential for male fertility and an attractive target for male contraception
The Na+ and K+ transport system of sperm (ATP1A4) is essential for male fertility and an attractive target for male contraception
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DOI：
10.1093/biolre/ioaa093
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发表时间：
2020-08-01
影响因子：
3.6
通讯作者：
Georg, Gunda, I
中科院分区：
文献类型：
--
作者：
Syeda, Shameem Sultana;Sanchez, Gladis;Georg, Gunda, I
细胞为完成其特殊任务而发展的机制之一是表达具有独特功能特性的特定蛋白质的不同分子变体。Na，K- atp酶（NKA）是维持细胞膜上Na+和K+跨膜浓度的离子运输机制，是具有高度分子和功能异质性的蛋白质系统之一。NKA催化亚基的四种不同亚型在哺乳动物细胞中表达（NKA α 1、NKA α 2、NKA α 3和NKA α 4）。NKA α 4 （ATP1A4）是表达模式最受限制的亚型，仅在睾丸的男性生殖细胞中产生。NKA α 4在精子中含量丰富，是精子运动和过度激活所必需的。本文就NKA α 4在精子生理中的表达、功能特性、作用机制及其在男性生育中的作用进行综述。此外，我们描述了将NKA α 4作为男性避孕的靶点，以及从药理学上阻断其离子转运功能以干扰男性生育能力的潜在方法。
One of the mechanisms that cells have developed to fulfil their specialized tasks is to express different molecular variants of a particular protein that has unique functional properties. Na,K-ATPase (NKA), the ion transport mechanism that maintains the transmembrane Na+ and K+ concentrations across the plasma membrane of cells, is one of such protein systems that shows high molecular and functional heterogeneity. Four different isoforms of the NKA catalytic subunit are expressed in mammalian cells (NKA alpha 1, NKA alpha 2, NKA alpha 3, and NKA alpha 4). NKA alpha 4 (ATP1A4) is the isoform with the most restricted pattern of expression, being solely produced in male germ cells of the testis. NKA alpha 4 is abundant in spermatozoa, where it is required for sperm motility and hyperactivation. This review discusses the expression, functional properties, mechanism of action of NKA alpha 4 in sperm physiology, and its role in male fertility. In addition, we describe the use of NKA alpha 4 as a target for male contraception and a potential approach to pharmacologically block its ion transport function to interfere with male fertility.