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

J. Biol. Chem., Vol. 281, Issue 40, 30046-30056, October 6, 2006

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 281/40/30046    most recent M602155200v1 Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bedet, C. Articles by Vannier, C. Search for Related Content PubMed PubMed Citation Articles by Bedet, C. Articles by Vannier, C. Social Bookmarking                      What's this?

Regulation of Gephyrin Assembly and Glycine Receptor Synaptic Stability^*

From the INSERM U789, the Laboratoire de Biologie Cellulaire de la Synapse, Ecole Normale Supérieure, F-75005, Paris, France

Gephyrin is required for the formation of clusters of the glycine receptor (GlyR) in the neuronal postsynaptic membrane. It can make trimers and dimers through its N- and C-terminal G and E domains, respectively. Gephyrin oligomerization could thus create a submembrane lattice providing GlyR-binding sites. We investigated the relationships between the stability of cell surface GlyR and the ability of gephyrin splice variants to form oligomers. Using truncated and full-length gephyrins we found that the 13-amino acid sequence (cassette 5) prevents G domain trimerization. Moreover, E domain dimerization is inhibited by the gephyrin central L domain. All of the gephyrin variants bind GlyR subunit cytoplasmic loop with high affinity regardless of their cassette composition. Coexpression experiments in COS-7 cells demonstrated that GlyR bound to gephyrin harboring cassette 5 cannot be stabilized at the cell surface. This gephyrin variant was found to deplete synapses from both GlyR and gephyrin in transfected neurons. These data suggest that the relative expression level of cellular variants influence the overall oligomerization pattern of gephyrin and thus the turnover of synaptic GlyR.

Received for publication, March 7, 2006 , and in revised form, June 14, 2006.

^* This work was supported by grants from the Association Française contre les Myopathies and from the Institut de Recherche sur la Moelle Epinière. 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.

The on-line version of this article (available at http://www.jbc.org) contains supplemental text and figures.

¹ Supported by the Institut National de la Santé et de la Recherche Médicale.

² To whom correspondence should be addressed: Laboratoire de Biologie Cellulaire de la Synapse Normale et Pathologique, INSERM U789, Ecole Normale Supérieure, 46 rue d'Ulm, 75005 Paris, France. Tel.: 33-1-44-32-35-36; Fax: 33-1-44-32-36-54; E-mail: vannier{at}wotan.ens.fr.

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

This article has been cited by other articles:

				B. Smolinsky, S. A. Eichler, S. Buchmeier, J. C. Meier, and G. Schwarz Splice-specific Functions of Gephyrin in Molybdenum Cofactor Biosynthesis J. Biol. Chem., June 20, 2008; 283(25): 17370 - 17379. [Abstract] [Full Text] [PDF]

				M.-V. Ehrensperger, C. Hanus, C. Vannier, A. Triller, and M. Dahan Multiple Association States between Glycine Receptors and Gephyrin Identified by SPT Analysis Biophys. J., May 15, 2007; 92(10): 3706 - 3718. [Abstract] [Full Text] [PDF]

				B. Lardi-Studler, B. Smolinsky, C. M. Petitjean, F. Koenig, C. Sidler, J. C. Meier, J.-M. Fritschy, and G. Schwarz Vertebrate-specific sequences in the gephyrin E-domain regulate cytosolic aggregation and postsynaptic clustering J. Cell Sci., April 15, 2007; 120(8): 1371 - 1382. [Abstract] [Full Text] [PDF]

				T. Saiyed, I. Paarmann, B. Schmitt, S. Haeger, M. Sola, G. Schmalzing, W. Weissenhorn, and H. Betz Molecular Basis of Gephyrin Clustering at Inhibitory Synapses: ROLE OF G- AND E-DOMAIN INTERACTIONS J. Biol. Chem., February 23, 2007; 282(8): 5625 - 5632. [Abstract] [Full Text] [PDF]