title: ClC-5: Physiological role and biophysical mechanisms.
abstract: Cl(-) transport in animal cells has fundamental physiological roles and it is mediated by a variety of protein families, one of them being the CLC family of ion channels and transporters. Besides their physiological relevance, CLC proteins show peculiar biophysical properties. This review will focus on a member of the CLC protein family, the endosomal Cl(-)/H(+) antiporter ClC-5. ClC-5 mutations cause Dent's disease, a renal syndrome due to defective protein reabsorption in the proximal tubule. This established the critical function of ClC-5 for endocytosis. However, our understanding of ClC-5's molecular role in endosomes and of its biophysical properties has proved elusive in spite of important progress achieved in the last two decades. Early models in which ClC-5 would provide a shunt conductance to enable efficient endosomal acidification conflicted with the antiport activity of ClC-5 that has more recently emerged. Currently, the physiological role of ClC-5 is hotly debated and its biophysical properties are still not fully understood.
authors.affiliation: Istituto di Biofisica, CNR, Via De Marini 6, 16149 Genoa, Italy.
authors.forename: Michael
authors.initials: M
authors.lastname: Pusch
authors.affiliation: Istituto di Biofisica, CNR, Via De Marini 6, 16149 Genoa, Italy. Electronic address: zifarelli@ge.ibf.cnr.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Zifarelli
mesh_terms: D000818:Animals; D018118:Chloride Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D057973:Dent Disease / Q000378:metabolism / Q000473:pathology; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D017136:Ion Transport; D017434:Protein Structure, Tertiary; D025262:Vacuolar Proton-Translocating ATPases / Q000737:chemistry / Q000378:metabolism
chemical_list: C097503:CLC-5 chloride channel; D018118:Chloride Channels; D025262:Vacuolar Proton-Translocating ATPases
keywords: Chloride transport; Dent's disease; Endocytosis; Endosome; Gating; Transporter