Thirty years of the NaCl cotransporter: from cloning to physiology and structure.

IF 3.7 2区 医学 Q1 PHYSIOLOGY
Gerardo Gamba
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引用次数: 0

Abstract

The primary structure of the thiazide-sensitive NaCl cotransporter (NCC) was resolved 30 years ago by the molecular identification of the cDNA encoding this cotransporter, from the winter's flounder urinary bladder, following a functional expression strategy. This review outlines some aspects of how the knowledge about thiazide diuretics and NCC evolved, the history of the cloning process, and the expansion of the SLC12 family of electroneutral cotransporters. The diseases associated with activation or inactivation of NCC are discussed, as well as the molecular model by which the activity of NCC is regulated. The controversies in the field are discussed as well as recent publication of the three-dimensional model of NCC obtained by cryo-electron microscopy, revealing not only the amino acid residues critical for Na+ and Cl- translocation but also the residues critical for polythiazide binding to the transporter, opening the possibility for a new era in thiazide diuretic therapy.

NaCl协同转运蛋白的三十年:从克隆到生理和结构。
30年前,通过对冬季牙鲆膀胱中编码该协同转运蛋白的cDNA的分子鉴定,按照功能表达策略,解析了噻嗪敏感的NaCl协同转运蛋白(NCC)的一级结构。这篇综述概述了关于噻嗪类利尿剂和NCC的知识是如何演变的,克隆过程的历史,以及SLC12电子共转运蛋白家族的扩展。讨论了与NCC激活或失活相关的疾病,以及调节NCC活性的分子模型。讨论了该领域的争议,以及最近通过冷冻电子显微镜获得的NCC三维模型的发表,该模型不仅揭示了对Na+和Cl-转运至关重要的氨基酸残基,还揭示了对聚噻嗪与转运蛋白结合至关重要的残基,为噻嗪利尿剂治疗开辟了新时代的可能性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
8.40
自引率
7.10%
发文量
154
审稿时长
2-4 weeks
期刊介绍: The American Journal of Physiology - Renal Physiology publishes original manuscripts on timely topics in both basic science and clinical research. Published articles address a broad range of subjects relating to the kidney and urinary tract, and may involve human or animal models, individual cell types, and isolated membrane systems. Also covered are the pathophysiological basis of renal disease processes, regulation of body fluids, and clinical research that provides mechanistic insights. Studies of renal function may be conducted using a wide range of approaches, such as biochemistry, immunology, genetics, mathematical modeling, molecular biology, as well as physiological and clinical methodologies.
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