ClC - Chloride Carrier/Channel
The Chloride Carrier/Channel Family is a large but poorly understood family consisting of several hundred sequenced proteins from bacteria and eucaryotes. Although structurally similar, the individual proteins act either as chloride channels or as chloride/proton exchangers. Most CIC proteins are located in the plasma membrane, but several are predominantly in intracellular membranes.
The mammalian CLC family contains 9 members, four of them (CIC-1, ClC-2, ClC-Ka, and ClC-Kb) are located on the plasma membrane where they act as chloride ion channels whereas the remaining five are located in intracellular organelles (CIC-3-7) and are chloride-proton exchangers. There is also a wide variety of bacterial CLC types.
The structures of two bacterial and one eukaryotic ClC proteins have been reported so far. CLS subunits have a complex topology of up to 18 transmembrane segments and form homodimers. However, each of the identical subunits contributes an individually functional ion transport pathway.
ClC Cl- channels have roles in the control of electrical excitability, extra- and intracellular ion homeostasis, and transepithelial transport, whereas anion/proton exchangers influence vesicular ion composition and impinge on endocytosis and lysosomal function. The surprisingly diverse roles of CLCs are highlighted by human and mouse disorders elicited by mutations in their genes. These pathologies include neurodegeneration, leukodystrophy, mental retardation, deafness, blindness, myotonia, hyperaldosteronism, renal salt loss, proteinuria, kidney stones, male infertility, and osteopetrosis.1
1. Saier Lab. Group, Transporter Classification Database