title: GlialCAM, a CLC-2 Cl(-) channel subunit, activates the slow gate of CLC chloride channels.
abstract: GlialCAM, 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.
authors.affiliation: Istituto di Biofisica, Consiglio Nazionale delle Ricerche, 16149 Genoa, Italy; Departments of Anesthesia and Biomedizin, ZLF Lab 408, Universitätsspital Basel, Switzerland.
authors.forename: Elena
authors.initials: E
authors.lastname: Jeworutzki
authors.affiliation: Istituto di Biofisica, Consiglio Nazionale delle Ricerche, 16149 Genoa, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Lagostena
authors.affiliation: Physiology Section, Department of Physiological Sciences II, School of Medicine, Barcelona, Spain; U-750, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Barcelona, Spain.
authors.forename: Xabier
authors.initials: X
authors.lastname: Elorza-Vidal
authors.affiliation: Physiology Section, Department of Physiological Sciences II, School of Medicine, Barcelona, Spain; U-750, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Barcelona, Spain; Department of Molecular Pharmacology and Cell Biology, FMP, Berlin, Germany.
authors.forename: Tania
authors.initials: T
authors.lastname: López-Hernández
authors.affiliation: Physiology Section, Department of Physiological Sciences II, School of Medicine, Barcelona, Spain; U-750, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Barcelona, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Estévez
authors.affiliation: Istituto di Biofisica, Consiglio Nazionale delle Ricerche, 16149 Genoa, Italy. Electronic address: pusch@ge.ibf.cnr.it.
authors.forename: Michael
authors.initials: M
authors.lastname: Pusch
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007477:Ions / Q000737:chemistry; D007700:Kinetics; D008564:Membrane Potentials / Q000502:physiology; D009154:Mutation; D009865:Oocytes; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D013696:Temperature; D014101:Torpedo; D014162:Transfection; D014982:Xenopus laevis; D015032:Zinc / Q000737:chemistry
chemical_list: D018797:Cell Cycle Proteins; D018118:Chloride Channels; C487620:HEPACAM protein, human; D007477:Ions; D011506:Proteins; D015032:Zinc