Referenced in: none

Automatically associated channels: ClC4 , ClC5

Title: A role for CBS domain 2 in trafficking of chloride channel CLC-5.

Authors: Georgina Carr, Nicholas Simmons, John Sayer

Journal, date & volume: Biochem. Biophys. Res. Commun., 2003 Oct 17 , 310, 600-5

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/14521953

Abstract
CLC-5 is a member of the CLC family of voltage-gated chloride channels. Mutations disrupting CLC-5 lead to Dent's disease, an X-linked renal tubular disorder, characterised by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, and renal stones. Sequence analysis of CLC-5 reveals a 746 amino acid protein with an intracellular amino-terminus, transmembrane spanning domains, and two CBS domains within its intracellular carboxy-terminus. CBS domains have been implicated in intracellular targetting and trafficking as well as protein-protein interactions. We investigate subcellular localisation of three naturally occurring CLC-5 mutants which all lead to a truncated protein, disrupting the second CBS domain. These mutants are unable to traffic normally to acidic endosomes but are retained in perinuclear compartments, colocalising with the Golgi complex. This is the first identification of the cellular pathogenesis of CBS domain mutations of CLC-5.