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CLC chloride channels and transporters: from genes to protein structure, pathology and physiology

Item Type:Review
Title:CLC chloride channels and transporters: from genes to protein structure, pathology and physiology
Creators Name:Jentsch, T.J.
Abstract:CLC genes are expressed in species from bacteria to human and encode Cl(-)-channels or Cl(-)/H(+)-exchangers. CLC proteins assemble to dimers, with each monomer containing an ion translocation pathway. Some mammalian isoforms need essential beta -subunits (barttin and Ostm1). Crystal structures of bacterial CLC Cl(-)/H(+)-exchangers, combined with transport analysis of mammalian and bacterial CLCs, yielded surprising insights into their structure and function. The large cytosolic carboxy-termini of eukaryotic CLCs contain CBS domains, which may modulate transport activity. Some of these have been crystallized. Mammals express nine CLC isoforms that differ in tissue distribution and subcellular localization. Some of these are plasma membrane Cl(-) channels, which play important roles in transepithelial transport and in dampening muscle excitability. Other CLC proteins localize mainly to the endosomal-lysosomal system where they may facilitate luminal acidification or regulate luminal chloride concentration. All vesicular CLCs may be Cl(-)/H(+)-exchangers, as shown for the endosomal ClC-4 and -5 proteins. Human diseases and knockout mouse models have yielded important insights into their physiology and pathology. Phenotypes and diseases include myotonia, renal salt wasting, kidney stones, deafness, blindness, male infertility, leukodystrophy, osteopetrosis, lysosomal storage disease and defective endocytosis, demonstrating the broad physiological role of CLC-mediated anion transport.
Keywords:Bartter Syndrome, Dent's Disease, Antiport, Anion Transport, ostm1, NCL, pH, Animals
Source:Critical Reviews in Biochemistry and Molecular Biology
Publisher:Taylor & Francis
Page Range:3-36
Date:January 2008
Additional Information:Erratum in: Crit Rev Biochem Mol Biol 44(4): 243-244.
Official Publication:https://doi.org/10.1080/10409230701829110
PubMed:View item in PubMed

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