QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, September 19, 2007, 27(38):10165-10175; doi:10.1523/JNEUROSCI.1772-07.2007

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter 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 Web of Science 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 Web of Science (24) Citing Articles via Google Scholar Google Scholar Articles by Groc, L. Articles by Chavis, P. Search for Related Content PubMed PubMed Citation Articles by Groc, L. Articles by Chavis, P.

 Previous Article  |  Next Article 

Cellular/Molecular
NMDA Receptor Surface Trafficking and Synaptic Subunit Composition Are Developmentally Regulated by the Extracellular Matrix Protein Reelin

Laurent Groc,² Daniel Choquet,² F. Anne Stephenson,³ Danièle Verrier,¹ Olivier J. Manzoni,¹ and Pascale Chavis¹

¹Inserm, Unité 862, Equipe Physiopathologie de la Plasticité Synaptique, 33077 Bordeaux Cedex, France, ²Physiologie Cellulaire de la Synapse, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5091, 33077 Bordeaux, France, and ³School of Pharmacy, University of London, London WC1N 1AX, United Kingdom

Correspondence should be addressed to either of the following: Pascale Chavis, Inserm, Unité 862, 146 rue Leo Saignat, 33077 Bordeaux Cedex, France, Email: chavis{at}bordeaux.inserm.fr; or Laurent Groc, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5091, 33077 Bordeaux Cedex, France, Email: laurent.groc{at}u-bordeaux2.fr

During postnatal development, changes in the subunit composition of glutamate receptors of the NMDA subtype (NMDARs) are key to the refinement of excitatory synapses. Hypotheses for maturation of synaptic NMDARs include regulation of their expression levels, membrane targeting, and surface movements. In addition, several members of extracellular matrix (ECM) proteins such as Reelin are involved in synaptic plasticity. However, it is not known whether and how ECM proteins regulate synaptic NMDAR maturation. To probe the participation of NMDARs to synaptic currents and NMDARs surface dynamics, we used electrophysiological recordings and single-particle tracking in cultured hippocampal neurons. Our results show that, during maturation, Reelin orchestrates the regulation of subunit composition of synaptic NMDARs and controls the surface mobility of NR2B subunits. During postnatal maturation, we observed a marked decrease of NR1/NR2B receptor participation to NMDAR-mediated synaptic currents concomitant with the accumulation of Reelin at active synapses. Blockade of the function of Reelin prevented the maturation-dependent reduction in NR1/NR2B-mediated synaptic currents. The reduction of NR1/NR2B receptors was not inhibited by blocking synaptic activity but required ß1-containing integrin receptors. Single-particle tracking showed that inhibition of Reelin decreased the surface mobility of native NR2B-containing NMDARs, whereas their synaptic dwell time increased. Conversely, recombinant Reelin dramatically reduced NR2B-mediated synaptic currents and the time spent by NR2B subunits within synapses. Our data reveal a new mode of control of synaptic NMDAR assembly at postnatal hippocampal synapses and an unprecedented role of ECM proteins in regulating glutamate receptor surface diffusion.

Key words: NMDA receptor; Reelin; surface mobility; development; integrins; hippocampus

---

Received April 19, 2007; revised Aug. 1, 2007; accepted Aug. 2, 2007.

Correspondence should be addressed to either of the following: Pascale Chavis, Inserm, Unité 862, 146 rue Leo Saignat, 33077 Bordeaux Cedex, France, Email: chavis{at}bordeaux.inserm.fr; or Laurent Groc, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5091, 33077 Bordeaux Cedex, France, Email: laurent.groc{at}u-bordeaux2.fr

This article has been cited by other articles:

				C.J. Carter Schizophrenia Susceptibility Genes Directly Implicated in the Life Cycles of Pathogens: Cytomegalovirus, Influenza, Herpes simplex, Rubella, and Toxoplasma gondii Schizophr Bull, November 1, 2009; 35(6): 1163 - 1182. [Abstract] [Full Text] [PDF]

				M. S. Durakoglugil, Y. Chen, C. L. White, E. T. Kavalali, and J. Herz Reelin signaling antagonizes {beta}-amyloid at the synapse PNAS, September 15, 2009; 106(37): 15938 - 15943. [Abstract] [Full Text] [PDF]

				P. Michaluk, L. Mikasova, L. Groc, R. Frischknecht, D. Choquet, and L. Kaczmarek Matrix Metalloproteinase-9 Controls NMDA Receptor Surface Diffusion through Integrin {beta}1 Signaling J. Neurosci., May 6, 2009; 29(18): 6007 - 6012. [Abstract] [Full Text] [PDF]

				M. A. Beazely, A. Lim, H. Li, C. Trepanier, X. Chen, B. Sidhu, and J. F. MacDonald Platelet-derived Growth Factor Selectively Inhibits NR2B-containing N-Methyl-D-aspartate Receptors in CA1 Hippocampal Neurons J. Biol. Chem., March 20, 2009; 284(12): 8054 - 8063. [Abstract] [Full Text] [PDF]

				L. Mikasova, L. Groc, D. Choquet, and O. J. Manzoni Altered surface trafficking of presynaptic cannabinoid type 1 receptor in and out synaptic terminals parallels receptor desensitization PNAS, November 25, 2008; 105(47): 18596 - 18601. [Abstract] [Full Text] [PDF]

				A. Scimemi Anchors aweigh: NMDA receptors set sail from their presynaptic port J. Physiol., October 15, 2008; 586(20): 4787 - 4787. [Full Text] [PDF]

				S. Niu, O. Yabut, and G. D'Arcangelo The Reelin Signaling Pathway Promotes Dendritic Spine Development in Hippocampal Neurons J. Neurosci., October 8, 2008; 28(41): 10339 - 10348. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help