Anno2014
AutoriJeworutzki, Elena; Lagostena, Laura; Elorza-Vidal, Xabier; Lopez-Hernandez, Tania; Estevez, Raul; Pusch, Michael
AbstractGlialCAM, a glial cell adhesion molecule mutated in megalencephalic leukoencephalopathy with subcortical cysts, targets the CLC-2 Cl- channel to cell contacts in glia and activates CLC-2 currents in vitro and in vivo. We found that GlialCAM clusters all CLC channels at cell contacts in vitro and thus studied GlialCAM interaction with CLC channels to investigate the mechanism of functional activation. GlialCAM slowed deactivation kinetics of CLC-Ka/barttin channels and increased CLC-0 currents opening the common gate and slowing its deactivation. No functional effect was seen for common gate deficient CLC-0 mutants. Similarly, GlialCAM targets the common gate deficient CLC-2 mutant E211V/H816A to cell contacts, without altering its function. Thus, GlialCAM is able to interact with all CLC channels tested, targeting them to cell junctions and activating them by stabilizing the open configuration of the common gate. These results are important to better understand the physiological role of GlialCAM/CLC-2 interaction.
RivistaBiophysical Journal (print)
ISSN0006-3495
Impact factor0
Volume107
Pagina inizio1105
Pagina fine1116
Autori IBFMichael PUSCH, Elena JEWORUTZKI, Laura LAGOSTENA
Linee di Ricerca IBFMD.P01.009.001
Sedi IBFIBF.GE