Affiliation:
1. Department of Medicinal Chemistry, College of Pharmacy, Institute for Therapeutics Discovery and Development, University of Minnesota, Minneapolis, MN 55414, USA
2. Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA
Abstract
AbstractOne 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 (NKAα1, NKAα2, NKAα3, and NKAα4). NKAα4 (ATP1A4) is the isoform with the most restricted pattern of expression, being solely produced in male germ cells of the testis. NKAα4 is abundant in spermatozoa, where it is required for sperm motility and hyperactivation. This review discusses the expression, functional properties, mechanism of action of NKAα4 in sperm physiology, and its role in male fertility. In addition, we describe the use of NKAα4 as a target for male contraception and a potential approach to pharmacologically block its ion transport function to interfere with male fertility.
Funder
Contraception Research Branch
Eunice Kennedy Shriver National Institute of Child Health and Human Development
Publisher
Oxford University Press (OUP)
Subject
Cell Biology,General Medicine,Reproductive Medicine
Cited by
27 articles.
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