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

M. Mondin, V. Labrousse, E. Hosy, M. Heine, B. Tessier, F. Levet, C. Poujol, C. Blanchet, D. Choquet, O. Thoumine
Journal of Neuroscience. 2011-09-21; 31(38): 13500-13515
DOI: 10.1523/jneurosci.6439-10.2011

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1. J Neurosci. 2011 Sep 21;31(38):13500-15. doi: 10.1523/JNEUROSCI.6439-10.2011.

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

Mondin M(1), Labrousse V, Hosy E, Heine M, Tessier B, Levet F, Poujol C, Blanchet
C, Choquet D, Thoumine O.

Author information:
(1)Interdisciplinary Institute of Neurosciences, CNRS, UMR 5297, Université de
Bordeaux, 33077 Bordeaux, France.

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.

DOI: 10.1523/JNEUROSCI.6439-10.2011
PMID: 21940442 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus