HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 51, 39300-39307, December 22, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/51/39300    most recent M608272200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yevenes, G. E. Articles by Aguayo, L. G. Search for Related Content PubMed PubMed Citation Articles by Yevenes, G. E. Articles by Aguayo, L. G. Social Bookmarking                      What's this?

Molecular Determinants for G Protein Modulation of Ionotropic Glycine Receptors^*

Gonzalo E. Yevenes, Gustavo Moraga-Cid, Leonardo Guzmán, Svenja Haeger, Laerte Oliveira^¶, Juan Olate^||, Günther Schmalzing, and Luis G. Aguayo¹

From the Laboratory of Neurophysiology, Department of Physiology, University of Concepción, Concepción, Chile, the Department of Molecular Pharmacology, Medical School of the Technical University of Aachen, Aachen, Germany, the ^¶Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil, and the ^||Laboratory of Molecular Genetics, Department of Biochemistry and Molecular Biology, University of Concepción, Concepción, Chile

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 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 ₁ subunit that are critical for binding and functional modulation by G. Mutations within these sequences demonstrated that all of the residues detected are important for G modulation, although both motifs are necessary for full binding. Molecular modeling predicts that these sites are -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 subunit modulation on GlyRs and provide a new framework regarding the ligand-gated ion channel superfamily regulation by intracellular signaling.

Received for publication, August 29, 2006 , and in revised form, October 4, 2006.

^* This work was supported by the National Institute on Alcohol Abuse and Alcoholism Grant RO1 AA15150-01, FONDECYT Grant 1020475, CONICYT Grant AT-4040102, funds from the Andes Foundation, and Deutsche Forschungsgemeinschaft Grants Schm536/4-l and 4-2. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. of Physiology, University of Concepción, P.O. Box 160-C, Concepción, Chile. Tel.: 56-41-2203380; Fax: 56-41-2245975; E-mail: laguayo{at}udec.cl.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. Villmann, J. Oertel, Z.-L. Ma-Hogemeier, M. Hollmann, R. Sprengel, K. Becker, H.-G. Breitinger, and C.-M. Becker Functional Complementation of Glra1spd-ot, a Glycine Receptor Subunit Mutant, by Independently Expressed C-Terminal Domains J. Neurosci., February 25, 2009; 29(8): 2440 - 2452. [Abstract] [Full Text] [PDF]

				G. E. Yevenes, G. Moraga-Cid, R. W. Peoples, G. Schmalzing, and L. G. Aguayo A selective G{beta}{gamma}-linked intracellular mechanism for modulation of a ligand-gated ion channel by ethanol PNAS, December 23, 2008; 105(51): 20523 - 20528. [Abstract] [Full Text] [PDF]

				V. B. Caraiscos, R. P. Bonin, J. G. Newell, E. Czerwinska, J. F. Macdonald, and B. A. Orser Insulin Increases the Potency of Glycine at Ionotropic Glycine Receptors Mol. Pharmacol., May 1, 2007; 71(5): 1277 - 1287. [Abstract] [Full Text] [PDF]