Characterization of Dent's disease mutations of CLC-5 reveals a correlation between functional and cell biological consequences and protein structure.

ABSTRACT: Mutations of the human CLCN5 gene, which encodes the CLC-5 Cl(-)/H(+) exchanger, lead to Dent's disease. Mutations result in functional defects that range from moderate reductions to complete loss of whole cell currents, although the severity of the functional defect rarely correlates with the severity of the disease. To further elucidate the basis of CLC-5 mutations causing Dent's disease, we examined the functional and cell biological consequences of seven previously reported missense mutants, utilizing electrophysiological and cell biological techniques. This revealed three classes of Dent's disease-causing CLC-5 mutations. Class 1 mutations lead to endoplasmic reticulum retention and degradation of CLC-5. Class 2 mutations appear to have little effect on subcellular distribution of CLC

SUBMITTER: Smith AJ 

PROVIDER: S-EPMC2643861 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature