Structure, function, and regulation of the SLC4 NBCe1 transporter and its role in causing proximal renal tubular acidosis.
Structure, function, and regulation of the SLC4 NBCe1 transporter and its role in causing proximal renal tubular acidosis.
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DOI：
10.1097/mnh.0b013e328363ff43
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发表时间：
2013-09
影响因子：
3.2
通讯作者：
Zhu Q
中科院分区：
文献类型：
--
作者：
Kurtz I;Zhu Q
NBCe 1是一种膜转运蛋白，在肾脏酸碱生理学中起着关键作用，在我们对NBCe 1的结构和功能特性以及调控的理解方面取得了重大进展。NBCe 1-A介导近端小管中的基底外侧产电钠碱转运，并且是跨上皮碳酸氢盐吸收所必需的。NBCe 1突变导致常染色体隐性近端肾小管酸中毒（pRTA）。本文综述了这一领域的最新进展。NBCe 1的拓扑模型已经建立，提供了一个基础，为未来的结构-功能研究的转运蛋白。NBCe 1中的关键残基和区域在其结构、功能（底物转运、产电性）和调控中起关键作用。NBC 1突变如何导致pRTA的机制最近也得到了阐明。鉴于近端小管经上皮碳酸氢盐吸收在全身酸碱平衡中的重要作用，对NBCe 1-A的结构-功能特性的清楚理解是阐明pRTA中缺陷性经上皮碳酸氢盐转运机制的先决条件。
There has been significant progress in our understanding of the structural and functional properties and regulation of NBCe1, a membrane transporter that plays a key role in renal acid-base physiology. NBCe1-A mediates basolateral electrogenic sodium-base transport in the proximal tubule and is critically required for transepithelial bicarbonate absorption. Mutations in NBCe1 cause autosomal recessive proximal renal tubular acidosis (pRTA). The review summarizes recent advances in this area. A topological model of NBCe1 has been established that provides a foundation for future structure-functional studies of the transporter. Critical residues and regions have been identified in NBCe1 that play key roles in its structure, function (substrate transport, electrogenicity) and regulation. The mechanisms of how NBC1 mutations cause pRTA have also recently been elucidated. Given the important role of proximal tubule transepithelial bicarbonate absorption in systemic acid-base balance, a clear understanding of the structure-functional properties of the NBCe1-A is a prerequisite for elucidating the mechanisms of defective transepithelial bicarbonate transport in pRTA.