Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada.
Channels (Austin). 2008 Sep-Oct;2(5):329-36. doi: 10.4161/chan.2.5.6898.
Sodium proton exchangers (NHEs) constitute a large family of polytopic membrane protein transporters found in organisms across all domains of life. They are responsible for the exchange of protons for sodium ions. In archaea, bacteria, yeast and plants they provide increased salt tolerance by removing sodium in exchanger for extracellular protons. In humans they have a host of physiological functions, the most prominent of which is removal of intracellular protons in exchange for extracellular sodium. Human NHE is also involved in heart disease, cell growth and in cell differentiation. NHE's physiological roles and the intriguing pathological consequences of their actions, make them a very important target of structural and functional studies. There are nine isoforms identified to date in humans. This review provides a brief overview of the human NHE's physiological and pathological roles and cellular/tissue distribution, with special attention to the exemplar member NHE1. A summary of our knowledge to date of the structure and function of NHE1 is included focusing on a discussion of the recent discrepancies reported on the topology of NHE1. Finally we discuss a newly discovered relative of the NHE1 isoform, the Na(+)/Li(+) exchanger, focusing on its predicted topology and its potential roles in disease.
钠氢交换蛋白（NHEs）构成了一个庞大的多跨膜蛋白转运蛋白家族，存在于所有生命领域的生物中。它们负责质子与钠离子的交换。在古细菌、细菌、酵母和植物中，它们通过将钠离子交换为细胞外质子来提供更高的耐盐性。在人类中，它们具有多种生理功能，其中最突出的功能是通过交换细胞外的钠离子来去除细胞内的质子。人类 NHE 还参与心脏病、细胞生长和细胞分化。NHE 的生理作用及其作用的有趣病理后果，使它们成为结构和功能研究的一个非常重要的靶点。迄今为止，已在人类中鉴定出 9 种同工型。本文简要概述了人类 NHE 的生理和病理作用以及细胞/组织分布，特别关注范例成员 NHE1。本文还包括对 NHE1 结构和功能的最新认识的总结，重点讨论了最近报道的 NHE1 拓扑结构的差异。最后，我们讨论了 NHE1 同工型的一个新发现的相对物，即 Na(+)/Li(+) 交换体，重点讨论其预测的拓扑结构及其在疾病中的潜在作用。
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