Meima Marcel E, Mackley Jennifer R, Barber Diane L
Department of Cell and Tissue Biology, University of California San Francisco, San Francisco, California 94143, USA.
Curr Opin Nephrol Hypertens. 2007 Jul;16(4):365-72. doi: 10.1097/MNH.0b013e3281bd888d.
The sodium-hydrogen exchanger isoform-1 (NHE1) functions in intracellular pH and cell volume homeostasis by catalyzing an electroneutral exchange of extracellular sodium and intracellular hydrogen. Recent studies have revealed the structural functions of NHE1 as an anchor for actin filaments and a scaffold for an ensemble of signaling proteins. This review highlights how these functions contribute to NHE1 regulation of biochemical events and cell behaviors.
New data confirming nontransport structural functions of NHE1 suggest reexamining how NHE1 regulates cell functions. Cell survival, cell substrate adhesion, and organization of the actin cytoskeleton are confirmed to be regulated through actin anchoring by NHE1 and likely by NHE1-dependent scaffolding of signaling proteins. A role for NHE1 in mechanotransduction is emerging and a challenge of future studies is to determine whether structural functions of NHE1 are important for mechanoresponsiveness.
This review highlights evidence for the nontransport functions of NHE1 and describes how the structural functions are integrated with ion translocation to regulate a range of cellular processes. Nontransporting features of NHE1 are analogous to recently observed nonconducting actions of ion channels in regulating cell behaviors and represent an emerging paradigm of ion transporters as multifunctional proteins.
钠氢交换体1型（NHE1）通过催化细胞外钠与细胞内氢的电中性交换，在细胞内pH值和细胞体积稳态中发挥作用。最近的研究揭示了NHE1作为肌动蛋白丝的锚定物和一组信号蛋白的支架的结构功能。本综述重点介绍了这些功能如何有助于NHE1对生化事件和细胞行为的调控。
新数据证实了NHE1的非转运结构功能，这表明需要重新审视NHE1如何调节细胞功能。细胞存活、细胞与底物的粘附以及肌动蛋白细胞骨架的组织被证实是通过NHE1的肌动蛋白锚定作用以及可能通过NHE1依赖的信号蛋白支架作用来调节的。NHE1在机械转导中的作用正在显现，未来研究面临的一个挑战是确定NHE1的结构功能对机械反应性是否重要。
本综述重点介绍了NHE1非转运功能的证据，并描述了其结构功能如何与离子转运整合以调节一系列细胞过程。NHE1的非转运特性类似于最近观察到的离子通道在调节细胞行为中的非传导作用，代表了离子转运蛋白作为多功能蛋白的一种新兴范式。
