Proton block of the CLC-5 Cl-/H+ exchanger.
Proton block of the CLC-5 Cl-/H+ exchanger.
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DOI：
10.1085/jgp.201010428
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发表时间：
2010-06
期刊：
影响因子：
--
通讯作者：
Accardi A
中科院分区：
文献类型：
--
作者：
Picollo A;Malvezzi M;Accardi A
CLC-5 is a H+/Cl− exchanger that is expressed primarily in endosomes but can traffic to the plasma membrane in overexpression systems. Mutations altering the expression or function of CLC-5 lead to Dent’s disease. Currents mediated by this transporter show extreme outward rectification and are inhibited by acidic extracellular pH. The mechanistic origins of both phenomena are currently not well understood. It has been proposed that rectification arises from the voltage dependence of a H+ transport step, and that inhibition of CLC-5 currents by low extracellular pH is a result of a reduction in the driving force for exchange caused by a pH gradient. We show here that the pH dependence of CLC-5 currents arises from H+ binding to a single site located halfway through the transmembrane electric field and driving the transport cycle in a less permissive direction, rather than a reduction in the driving force. We propose that protons bind to the extracellular gating glutamate E211 in CLC-5. It has been shown that CLC-5 becomes severely uncoupled when SCN− is the main charge carrier: H+ transport is drastically reduced while the rate of anion movement is increased. We found that in these conditions, rectification and pH dependence are unaltered. This implies that H+ translocation is not the main cause of rectification. We propose a simple transport cycle model that qualitatively accounts for these findings.
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影响因子：
3.8
作者：
Accardi, Alessio;Walden, Michael;Nguitragool, Wang;Jayaram, Hariharan;Williams, Carole;Miller, Christopher
通讯作者：
Miller, Christopher
影响因子：
3.8
作者：
Engh, Anita M.;Faraldo-Gomez, Jose D.;Maduke, Merritt
通讯作者：
Maduke, Merritt
影响因子：
4.8
作者：
Zdebik, Anselm A.;Zifarelli, Giovanni;Pusch, Michael
通讯作者：
Pusch, Michael
影响因子：
64.8
作者：
Graves, Austin R.;Curran, Patricia K.;Mindell, Joseph A.
通讯作者：
Mindell, Joseph A.
DOI：
10.1016/j.bbrc.2005.02.060
发表时间：
2005-04-15
影响因子：
3.1
作者：
Hara-Chikuma, M;Wang, YH;Verkman, AS
通讯作者：
Verkman, AS