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

Yevenes, GE; Moraga-Cid, G; Guzman, L; Haeger, S; Oliveira L.; Olate, J; Schmalzing, G; Aguayo, LG

Abstract

The 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 βγ 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 α1 subunit that are critical for binding and functional modulation by Gβγ. Mutations within these sequences demonstrated that all of the residues detected are important for Gβγ modulation, although both motifs are necessary for full binding. Molecular modeling predicts that these sites are α-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 βγ subunit modulation on GlyRs and provide a new framework regarding the ligand-gated ion channel superfamily regulation by intracellular signaling. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.

Más información

Título según WOS: Molecular determinants for G protein beta gamma modulation of ionotropic glycine receptors
Título según SCOPUS: Molecular determinants for G protein ß? modulation of ionotropic glycine receptors
Título de la Revista: JOURNAL OF BIOLOGICAL CHEMISTRY
Volumen: 281
Número: 51
Editorial: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Fecha de publicación: 2006
Página de inicio: 39300
Página final: 39307
Idioma: English
URL: http://www.jbc.org/cgi/doi/10.1074/jbc.M608272200
DOI:

10.1074/jbc.M608272200

Notas: ISI, SCOPUS