Membrane surface charge dictates the structure and function of the epithelial Na+/H+ exchanger
Membrane surface charge dictates the structure and function of the epithelial Na+/H+ exchanger
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DOI：
10.1038/emboj.2010.356
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发表时间：
2011-02-16
期刊：
影响因子：
11.4
通讯作者：
Grinstein, Sergio
中科院分区：
文献类型：
--
作者：
Alexander, Robert Todd;Jaumouille, Valentin;Grinstein, Sergio
Na+/H+交换器NHE 3在血管内容量和酸碱平衡中起着核心作用。离子交换活性由其跨膜结构域赋予，而通过多种刺激调节转运速率取决于其胞质C-末端区域。脂质体和细胞为基础的测定采用合成或重组片段的胞质尾部表现出优先协会与阴离子膜，这是废除干扰静电相互作用的扰动。共振能量转移测量表明，C-末端结构域的部分接近双层。在完整的细胞中，通过诱变或破坏静电相互作用来中和胞质尾部的碱性残基，抑制Na+/H+交换活性。静电开关模型，提出了考虑多个方面的NHE 3活性的调节。The EMBO Journal（2011）30，679-691. doi：10.1038/doj.2010.356; 2011年1月18日在线发布
The Na+/H+ exchanger NHE3 plays a central role in intravascular volume and acid-base homeostasis. Ion exchange activity is conferred by its transmembrane domain, while regulation of the rate of transport by a variety of stimuli is dependent on its cytosolic C-terminal region. Liposome-and cell-based assays employing synthetic or recombinant segments of the cytosolic tail demonstrated preferential association with anionic membranes, which was abrogated by perturbations that interfere with electrostatic interactions. Resonance energy transfer measurements indicated that segments of the C-terminal domain approach the bilayer. In intact cells, neutralization of basic residues in the cytosolic tail by mutagenesis or disruption of electrostatic interactions inhibited Na+/H+ exchange activity. An electrostatic switch model is proposed to account for multiple aspects of the regulation of NHE3 activity. The EMBO Journal (2011) 30, 679-691. doi:10.1038/emboj.2010.356; Published online 18 January 2011