Molecular determinants for G protein beta gamma modulation of ionotropic glycine receptors

dc.contributor.authorYevenes, Gonzalo E.
dc.contributor.authorMoraga-Cid, Gustavo
dc.contributor.authorGuzman, Leonardo
dc.contributor.authorHaeger, Svenja
dc.contributor.authorOliveira, Laerte [UNIFESP]
dc.contributor.authorOlate, Juan
dc.contributor.authorSchmalzing, Gunther
dc.contributor.authorAguayo, Luis G.
dc.contributor.institutionUniv Concepcion
dc.contributor.institutionRhein Westfal TH Aachen
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.description.abstractThe ligand-gated ion channel superfamily plays a critical role in neuronal excitability. the functions of glycine receptor ( GlyR) and nicotinic acetylcholine receptor are modulated by G protein beta gamma subunits. the molecular determinants for this functional modulation, however, are still unknown. Studying mutant receptors, we identified two basic amino acid motifs within the large intracellular loop of the GlyR alpha(1) subunit that are critical for binding and functional modulation by G beta gamma. Mutations within these sequences demonstrated that all of the residues detected are important for G beta gamma modulation, although both motifs are necessary for full binding. Molecular modeling predicts that these sites are alpha-helixes near transmembrane domains 3 and 4, near to the lipid bilayer and highly electropositive. Our results demonstrate for the first time the sites for G protein beta gamma subunit modulation on GlyRs and provide a new framework regarding the ligand-gated ion channel superfamily regulation by intracellular signaling.en
dc.description.affiliationUniv Concepcion, Dept Physiol, Neurophysiol Lab, Concepcion, Chile
dc.description.affiliationRhein Westfal TH Aachen, Dept Mol Pharmacol, Aachen, Germany
dc.description.affiliationUniversidade Federal de São Paulo, Escola Paulista Med, São Paulo, Brazil
dc.description.affiliationUniv Concepcion, Dept Biochem & Mol Biol, Genet Mol Lab, Concepcion, Chile
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Escola Paulista Med, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.identifier.citationJournal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 281, n. 51, p. 39300-39307, 2006.
dc.publisherAmer Soc Biochemistry Molecular Biology Inc
dc.relation.ispartofJournal of Biological Chemistry
dc.rightsAcesso aberto
dc.titleMolecular determinants for G protein beta gamma modulation of ionotropic glycine receptorsen