Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication




Journal article



Publication Date





951 - 961


Animals, Biophysics, Cells, Cultured, Chloride Channels, Connexins, Electric Stimulation, Glial Fibrillary Acidic Protein, Green Fluorescent Proteins, Humans, Immunoprecipitation, Mass Spectrometry, Membrane Potentials, Mice, Mice, Transgenic, Microinjections, Microscopy, Confocal, Microscopy, Electron, Transmission, Models, Molecular, Mutation, Myelin Sheath, Myosin Light Chains, Neuroglia, Oocytes, Patch-Clamp Techniques, Protein Transport, Rats, Transfection, Xenopus