GlialCAM, a Protein Defective in a Leukodystrophy, Serves As a ClC-2 Cl(-) Channel Auxiliary Subunit

Overview

Journal Neuron

Publisher Cell Press

Specialty Neurology

Date 2012 Mar 13

PMID 22405205

Citations 77

Authors

Elena Jeworutzki

Tania Lopez-Hernandez

Xavier Capdevila-Nortes

Sonia Sirisi

Luiza Bengtsson

Marisol Montolio

Giovanni Zifarelli

Tanit Arnedo

Catrin S Muller

Uwe Schulte

Virginia Nunes

Albert Martinez

Thomas J Jentsch

Xavier Gasull

Michael Pusch

Raul Estevez

Affiliations

Soon will be listed here.

Abstract

Ion fluxes mediated by glial cells are required for several physiological processes such as fluid homeostasis or the maintenance of low extracellular potassium during high neuronal activity. In mice, the disruption of the Cl(-) channel ClC-2 causes fluid accumulation leading to myelin vacuolation. A similar vacuolation phenotype is detected in humans affected with megalencephalic leukoencephalopathy with subcortical cysts (MLC), a leukodystrophy which is caused by mutations in MLC1 or GLIALCAM. We here identify GlialCAM as a ClC-2 binding partner. GlialCAM and ClC-2 colocalize in Bergmann glia, in astrocyte-astrocyte junctions at astrocytic endfeet around blood vessels, and in myelinated fiber tracts. GlialCAM targets ClC-2 to cell junctions, increases ClC-2 mediated currents, and changes its functional properties. Disease-causing GLIALCAM mutations abolish the targeting of the channel to cell junctions. This work describes the first auxiliary subunit of ClC-2 and suggests that ClC-2 may play a role in the pathology of MLC disease.

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