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PMID: 21940442 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Neurexin-neuroligin adhesions capture surface-diffusing AMPA receptors through PSD-95 scaffolds.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 31 ·No. 38 ·2011-09-21 ·Pages 13500-15

Mondin M, Labrousse V, Hosy E, Heine M, Tessier B, Levet F, Poujol C, Blanchet C, Choquet D, Thoumine O

Abstract

The mechanisms governing the recruitment of functional glutamate receptors at nascent excitatory postsynapses following initial axon-dendrite contact remain unclear. We examined here the ability of neurexin/neuroligin adhesions to mobilize AMPA-type glutamate receptors (AMPARs) at postsynapses through a diffusion/trap process involving the scaffold molecule PSD-95. Using single nanoparticle tracking in primary rat and mouse hippocampal neurons overexpressing or lacking neuroligin-1 (Nlg1), a striking inverse correlation was found between AMPAR diffusion and Nlg1 expression level. The use of Nlg1 mutants and inhibitory RNAs against PSD-95 demonstrated that this effect depended on intact Nlg1/PSD-95 interactions. Furthermore, functional AMPARs were recruited within 1 h at nascent Nlg1/PSD-95 clusters assembled by neurexin-1β multimers, a process requiring AMPAR membrane diffusion. Triggering novel neurexin/neuroligin adhesions also caused a depletion of PSD-95 from native synapses and a drop in AMPAR miniature EPSCs, indicating a competitive mechanism. Finally, both AMPAR level at synapses and AMPAR-dependent synaptic transmission were diminished in hippocampal slices from newborn Nlg1 knock-out mice, confirming an important role of Nlg1 in driving AMPARs to nascent synapses. Together, these data reveal a mechanism by which membrane-diffusing AMPARs can be rapidly trapped at PSD-95 scaffolds assembled at nascent neurexin/neuroligin adhesions, in competition with existing synapses.

MeSH Terms
Animals Calcium-Binding Proteins Cell Adhesion Molecules, Neuronal/biosynthesis,genetics Disks Large Homolog 4 Protein Female Guanylate Kinases/antagonists & inhibitors,genetics,metabolism Hippocampus/metabolism,physiology Male Membrane Potentials/genetics,physiology Membrane Proteins/antagonists & inhibitors,genetics,metabolism Mice Mice, Knockout Mutation Neural Cell Adhesion Molecules/metabolism Patch-Clamp Techniques/methods Primary Cell Culture Rats Receptors, AMPA/metabolism,physiology Synaptic Transmission/genetics,physiology Transfection/methods
Chemicals
Calcium-Binding Proteins Cell Adhesion Molecules, Neuronal Disks Large Homolog 4 Protein Dlg4 protein, mouse Membrane Proteins Neural Cell Adhesion Molecules Nrxn1 protein, mouse Receptors, AMPA neuroligin 1 Guanylate Kinases
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Mondin Magali
Interdisciplinary Institute of Neurosciences, CNRS, UMR 5297, Université de Bordeaux, 33077 Bordeaux, France.
Labrousse Virginie
Hosy Eric
Heine Martin
Tessier Béatrice
Levet Florian
Poujol Christel
Blanchet Christophe
Choquet Daniel
Thoumine Olivier
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.6439-10.2011
Published
2011-09-21
Pages
13500-15
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6623291
Subset
IM
External Links
PubMed source DOI: 10.1523/JNEUROSCI.6439-10.2011 PMC Full Text View journal details
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