NMDA receptor surface trafficking and synaptic subunit composition are developmentally regulated by the extracellular matrix protein reelin
Journal of Neuroscience. 2007-09-19; 27(38): 10165-10175
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1. J Neurosci. 2007 Sep 19;27(38):10165-75.
NMDA receptor surface trafficking and synaptic subunit composition are
developmentally regulated by the extracellular matrix protein Reelin.
Groc L(1), Choquet D, Stephenson FA, Verrier D, Manzoni OJ, Chavis P.
(1)Physiologie Cellulaire de la Synapse, Centre National de la Recherche
Scientifique, Unité Mixte de Recherche 5091, 33077 Bordeaux, France.
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 beta1-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.
PMID: 17881522 [Indexed for MEDLINE]