Anno2012
AutoriJeworutzki E; Lopez-Hernandez T; Capdevila-Nortes X; Bengtsson L; Sirisi S; Montolio M; Zifarelli G; Arnedo T; Muller CS; Schulte U; Nunes V; Martinez A; Jentsch TJ; Gasull X; Pusch M; Estevez R
AbstractIon 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.
RivistaNeuron
ISSN0896-6273
Impact factor
Volume73
Pagina inizio961
Pagina fine951
Autori IBFMichael PUSCH, Giovanni ZIFARELLI, Elena JEWORUTZKI
Linee di Ricerca IBFMD.P01.009.001
Sedi IBFIBF.GE