{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:52:45Z","timestamp":1791996765808,"version":"4.4.0"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2007,1,26]],"date-time":"2007-01-26T00:00:00Z","timestamp":1169769600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2007,2]]},"abstract":"<jats:p>Several members of the CLC family of Cl<jats:sup>\u2212<\/jats:sup> channels and transporters are expressed in vesicles of the endocytotic\u2013lysosomal pathway, all of which are acidified by V\u2010type proton pumps. These CLC proteins are thought to facilitate vesicular acidification by neutralizing the electric current of the H<jats:sup>+<\/jats:sup>\u2010ATPase. Indeed, the disruption of ClC\u20105 impaired the acidification of endosomes, and the knock\u2010out (KO) of ClC\u20103 that of endosomes and synaptic vesicles. KO mice are available for all vesicular CLCs (ClC\u20103 to ClC\u20107), and ClC\u20105 and ClC\u20107, as well as its \u03b2\u2010subunit Ostm1, are mutated in human disease. The associated mouse and human pathologies, ranging from impaired endocytosis and nephrolithiasis (ClC\u20105) to neurodegeneration (ClC\u20103), lysosomal storage disease (ClC\u20106, ClC\u20107\/Ostm1) and osteopetrosis (ClC\u20107\/Ostm1), were crucial in identifying the physiological roles of vesicular CLCs. Whereas the intracellular localization of ClC\u20106 and ClC\u20107\/Ostm1 precluded biophysical studies, the partial expression of ClC\u20104 and \u20105 at the cell surface allowed the detection of strongly outwardly rectifying currents that depended on anions and pH. Surprisingly, ClC\u20104 and ClC\u20105 (and probably ClC\u20103) do not function as Cl<jats:sup>\u2212<\/jats:sup> channels, but rather as electrogenic Cl<jats:sup>\u2212<\/jats:sup>\u2013H<jats:sup>+<\/jats:sup> exchangers. This hints at an important role for luminal chloride in the endosomal\u2013lysosomal system.<\/jats:p>","DOI":"10.1113\/jphysiol.2006.124719","type":"journal-article","created":{"date-parts":[[2006,11,17]],"date-time":"2006-11-17T01:30:21Z","timestamp":1163727021000},"page":"633-640","source":"Crossref","is-referenced-by-count":211,"title":["Chloride and the endosomal\u2013lysosomal pathway: emerging roles of CLC chloride transporters"],"prefix":"10.1113","volume":"578","author":[{"given":"Thomas 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