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

Authors: Mondin, M  Labrousse, V  Hosy, E  Heine, M  Tessier, B  Levet, F  Poujol, C  Blanchet, C  Choquet, D  Thoumine, O 
Citation: Mondin M, etal., J Neurosci. 2011 Sep 21;31(38):13500-15. doi: 10.1523/JNEUROSCI.6439-10.2011.
Pubmed: (View Article at PubMed) PMID:21940442
DOI: Full-text: DOI:10.1523/JNEUROSCI.6439-10.2011

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-1beta 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.


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CRRD Object Information
CRRD ID: 8553843
Created: 2014-05-08
Species: All species
Last Modified: 2014-05-08
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.