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Chloride and the endosomal/lysosomal pathway: emerging roles of CLC chloride transporters

Item Type:Article
Title:Chloride and the endosomal/lysosomal pathway: emerging roles of CLC chloride transporters
Creators Name:Jentsch, T.J.
Abstract:Several members of the CLC family of Cl--channels and aeuro'transporters are expressed in vesicles of the endocytotic / lysomomal pathway, all of which are acidified by V-type proton pumps. These CLC proteins are thought to facilitate vesicular acidification by neutralizing the electric current of the H+-ATPase. Indeed, the disruption of ClC-5 impaired the acidification of endosomes, and the knock-out of ClC-3 that of endosomes and synaptic vesicles. Knock-out (KO) mice are available for all vesicular CLCs (ClC-3 through ClC-7), and ClC-5 and ClC-7, as well as its I(2)-subunit Ostm1, are mutated in human disease. The associated mouse and human pathologies, ranging from impaired endocytosis and nephrolithiasis (ClC-5) to neurodegeneration (ClC-3), lysosomal storage disease (ClC-6, ClC-7/Ostm1) and osteopetrosis (ClC-7/Ostm1), were crucial in identifying the physiological roles of vesicular CLCs. Whereas the intracellular localization of ClC-6 and ClC 7/Ostm1 precluded biophysical studies, the partial expression of ClC-4 and 5 at the cell surface allowed the detection of strongly outwardly-rectifying currents that depended on anions and pH. Surprisingly, ClC-4 and ClC-5 (and probably ClC-3) do not function as Cl- channels, but rather as electrogenic Cl-/H+-exchangers. This hints at an important role for luminal chloride in the endosomal/lysosomal system.
Keywords:Cl-channels, Endocytosis, Osteoclast, Animals, Mice
Source:Journal of Physiology
Publisher:Blackwell Publishing
Number:Pt 3
Page Range:633-640
Date:February 2007
Official Publication:https://doi.org/10.1113/jphysiol.2006.124719
PubMed:View item in PubMed

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