Regulation of ENaC expression at the cell surface by Rab11
Regulation of ENaC expression at the cell surface by Rab11
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DOI：
10.1016/j.bbrc.2008.10.014
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发表时间：
2008-12-12
影响因子：
3.1
通讯作者：
Staruschenko, Alexander
中科院分区：
文献类型：
--
作者：
Karpushev, Alexey V.;Levchenko, Vladislav;Staruschenko, Alexander
上皮性钠离子通道(ENaC)是钠离子重吸收的重要通道。与ENaC共表达Rab11a和Rab3a小G蛋白可显著增加通道活性。相反，共表达Rab5、Rab27a和Arf-1对ENaC活性无影响或略有降低。用PD98059抑制MEK，用Y27632抑制Rho-Kinase，用LY294002抑制PI3-Kinase，对Rab11a转基因CHO细胞的ENaC活性无明显影响。荧光成像方法证明Rab11a与ENaC共定位。Rab11a以显性-负性动力蛋白相加的方式增加ENaC的活性，这是一种负责内吞作用的GTP酶。胞内蛋白转位抑制剂Brefeldin A可阻断Rab11a对ENaC活性的刺激作用。我们得出结论，存在于顶端质膜上的ENaC通道正在以Rab11依赖的方式与细胞内池中的通道进行交换。(C)2008 Elsevier Inc.保留所有权利。
he epithelial Na+ channel (ENaC) is an essential channel responsible for Na+ reabsorption. Coexpression of Rab11a and Rab3a small G proteins with ENaC results in a significant increase in channel activity. In contrast, coexpression of Rab5, Rab27a, and Arf-1 had no effect or slightly decreased ENaC activity. Inhibition of MEK with PD98059, Rho-kinase with Y27632 or PI3-kinase with LY294002 had no effect on ENaC activity in Rab11a-transfected CHO cells. Fluorescence imaging methods demonstrate that Rab11a colocalized with ENaC. Rab11a increases ENaC activity in an additive manner with dominant-negative dynamin, which is a GTPase responsible for endocytosis. Brefeldin A, an inhibitor of intracellular protein translocation, blocked the stimulatory action of Rab11a on ENaC activity. We conclude that ENaC channels, present on the apical plasma membrane, are being exchanged with channels from the intracellular pool in a Rab11-dependent manner. (C) 2008 Elsevier Inc. All rights reserved.