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A Tale of Two CLCs: Biophysical Insights Toward Understanding ClC-5 and ClC-7 Function in Endosomes and Lysosomes

Overview
Journal J Physiol
Specialty Physiology
Date 2015 Jun 4
PMID 26036722
Citations 12
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Abstract

The CLC protein family comprises both Cl(-) channels and H(+) -coupled anion transporters. The understanding of the critical role of CLC proteins in a number of physiological functions has greatly contributed to a revision of the classical paradigm that attributed to Cl(-) ions only a marginal role in human physiology. The endosomal ClC-5 and the lysosomal ClC-7 are the best characterized human CLC transporters. Their dysfunction causes Dent's disease and osteopetrosis, respectively. It had been originally proposed that they would provide a Cl(-) shunt conductance allowing efficient acidification of intracellular compartments. However, this model seems to conflict with the transport properties of these proteins and with recent physiological evidence. Currently, there is no consensus on their specific physiological role. CLC proteins present also a number of peculiar biophysical properties, such as the dimeric architecture, the co-existence of intrinsically different thermodynamic modes of transport based on similar structural principles, and the gating mechanism recently emerging for the transporters, just to name a few. This review focuses on the biophysical properties and physiological roles of ClC-5 and ClC-7.

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References
1.
Stauber T, Weinert S, Jentsch T . Cell biology and physiology of CLC chloride channels and transporters. Compr Physiol. 2013; 2(3):1701-44. DOI: 10.1002/cphy.c110038. View

2.
Accardi A, Pusch M . Conformational changes in the pore of CLC-0. J Gen Physiol. 2003; 122(3):277-93. PMC: 2234480. DOI: 10.1085/jgp.200308834. View

3.
Lisal J, Maduke M . The ClC-0 chloride channel is a 'broken' Cl-/H+ antiporter. Nat Struct Mol Biol. 2008; 15(8):805-10. PMC: 2559860. DOI: 10.1038/nsmb.1466. View

4.
Alekov A, Fahlke C . Channel-like slippage modes in the human anion/proton exchanger ClC-4. J Gen Physiol. 2009; 133(5):485-96. PMC: 2712972. DOI: 10.1085/jgp.200810155. View

5.
Lobet S, Dutzler R . Ion-binding properties of the ClC chloride selectivity filter. EMBO J. 2005; 25(1):24-33. PMC: 1356352. DOI: 10.1038/sj.emboj.7600909. View