Activity-independent and subunit-specific recruitment of functional AMPA receptors at neurexin/neuroligin contacts.
Proceedings of the National Academy of Sciences. 2008-12-19; 105(52): 20947-20952
DOI: 10.1073/pnas.0804007106
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1. Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20947-52. doi:
10.1073/pnas.0804007106. Epub 2008 Dec 19.
Activity-independent and subunit-specific recruitment of functional AMPA
receptors at neurexin/neuroligin contacts.
Heine M(1), Thoumine O, Mondin M, Tessier B, Giannone G, Choquet D.
Author information:
(1)Centre National de la Recherche Scientifique UMR 5091, Physiologie Cellulaire
de la Synapse, Institut François Magendie, Université Bordeaux 2, 33077 Bordeaux,
France.
A combination of cell culture and animal studies has recently shown that adhesion
between neurexins and neuroligins played important roles in synapse initiation,
maturation, and function. Binding of neurexin-1beta to neuroligin-1 triggers the
postsynaptic clustering of the scaffold postsynaptic density protein 95, but the
composition and timing of accumulation of glutamate receptors at those nascent
contacts remain unclear. Using glutamate iontophoresis and patch-clamp
recordings, we identified functional AMPA receptors (AMPARs) and NMDA receptors
at postsynaptic density protein 95 clusters induced by neurexin-1beta coated
microspheres on primary hippocampal neurons. The recruitment of AMPARs occurred
as early as 2 h after initial contact, and was not blocked by
TTX/2-amino-5-phosphovaleric acid (APV) treatment. The differential recruitment
of recombinant subunits GluR1 and GluR2, as well as the absence of rectification
in voltage/current curves, further indicate that neurexin/neuroligin contacts
primarily recruit GluR2-containing AMPARs. Finally, by using glutamate un-caging
and calcium imaging, we show that AMPARs participate in calcium entry at
neurexin-1beta induced post-synapses, most likely through the activation of
voltage-gated calcium channels. Such rapid and activity-independent accumulation
of functional AMPARs at neurexin-1beta-induced postsynapses points to a new role
of AMPARs in synaptogenesis.
DOI: 10.1073/pnas.0804007106
PMCID: PMC2634880
PMID: 19098102 [Indexed for MEDLINE]