Voltage-dependent electrogenic chloride/proton exchange by endosomal CLC proteins
Voltage-dependent electrogenic chloride/proton exchange by endosomal CLC proteins
复制标题
DOI：
10.1038/nature0386o
复制
发表时间：
2005-07-21
期刊：
影响因子：
64.8
通讯作者：
Jentsch, TJ
中科院分区：
文献类型：
--
作者：
Scheel, O;Zdebik, AA;Jentsch, TJ
Eukaryotic members of the CLC gene family function as plasma membrane chloride channels, or may provide neutralizing anion currents for V-type H+-ATPases that acidify compartments of the endosomal/lysosomal pathway(1). Loss-of-function mutations in the endosomal protein ClC-5 impair renal endocytosis(2) and lead to kidney stones(3), whereas loss of function of the endosomal/ lysosomal protein ClC-7 entails osteopetrosis(4) and lysosomal storage disease(5). Vesicular CLCs have been thought to be Cl- channels, in particular because ClC-4 and ClC-5 mediate plasma membrane Cl- currents upon heterologous expression(6,7). Here we show that these two mainly endosomal CLC proteins instead function as electrogenic Cl-/H+ exchangers ( also called antiporters), resembling the transport activity of the bacterial protein ClC-e1 ( ref. 8), the crystal structure of which has already been determined(9). Neutralization of a critical glutamate residue not only abolished the steep voltage-dependence of transport(7), but also eliminated the coupling of anion flux to proton counter-transport. ClC-4 and ClC-5 may still compensate the charge accumulation by endosomal proton pumps, but are expected to couple directly vesicular pH gradients to Cl- gradients.
