Neuron (Cambridge, Mass.), 2012-03, Vol.73 (5), p.951-961
2012
Details
- Autor(en) / Beteiligte
- Titel
- GlialCAM, a Protein Defective in a Leukodystrophy, Serves as a ClC-2 Cl− Channel Auxiliary Subunit
- Ist Teil von
- Neuron (Cambridge, Mass.), 2012-03, Vol.73 (5), p.951-961
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2012
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. [Display omitted] ► GlialCAM, which is defective in MLC disease, is a ClC-2 Cl− channel subunit ► GlialCAM modifies the targeting and the functional activity of the ClC-2 channel ► Mutations found in GLIALCAM in MLC affect the targeting of ClC-2 to cell junctions Leukodystrophies are a group of genetic diseases affecting white matter. Jeworutzki et al. find that GlialCAM, a cell-adhesion molecule which is mutated in a leukodystrophy, serves as an auxiliary subunit of the chloride channel ClC-2.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0896-6273eISSN: 1097-4199DOI: 10.1016/j.neuron.2011.12.039Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3334819
- Format
- –
- Schlagworte
- Animals, Biophysics, Cells, Cultured, Chloride Channels - genetics, Chloride Channels - physiology, Chloride Channels - ultrastructure, Connexins - metabolism, Cysts, Electric Stimulation, Experiments, Glial Fibrillary Acidic Protein - metabolism, Green Fluorescent Proteins - genetics, Green Fluorescent Proteins - metabolism, Homeostasis, Humans, Immunoprecipitation, Kinases, Mass Spectrometry, Membrane Potentials - drug effects, Membrane Potentials - genetics, Mice, Mice, Transgenic, Microinjections - methods, Microscopy, Confocal, Microscopy, Electron, Transmission, Models, Molecular, Mutation, Mutation - genetics, Myelin Sheath - metabolism, Myelin Sheath - ultrastructure, Myosin Light Chains - genetics, Neuroglia - metabolism, Neuroglia - ultrastructure, Oocytes, Patch-Clamp Techniques, Protein Transport - genetics, Proteins, Rats, Rodents, Transfection, Xenopus