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The Journal of Neuroscience, August 15, 2001, 21(16):6058-6068
Activation of Metabotropic Glutamate Receptor 1 Accelerates NMDA
Receptor Trafficking
Jian-yu
Lan,
Vytenis A.
Skeberdis,
Teresa
Jover,
Xin
Zheng,
Michael V. L.
Bennett, and
R. Suzanne
Zukin
Department of Neuroscience, Albert Einstein College of Medicine,
Bronx, New York 10461
Regulation of neuronal NMDA receptors (NMDARs) by group I
metabotropic glutamate receptors (mGluRs) is known to play a critical role in synaptic transmission. The molecular mechanisms underlying mGluR1-mediated potentiation of NMDARs are as yet unclear. The present
study shows that in Xenopus oocytes expressing
recombinant receptors, activation of mGluR1 potentiates NMDA channel
activity by recruitment of new channels to the plasma membrane via
regulated exocytosis. Activation of mGluR1 induced (1) an increase
in channel number times channel open probability, with no change in
mean open time, unitary conductance, or reversal potential; (2) an increase in charge transfer in the presence of NMDA and the open channel blocker MK-801, indicating an increased number of
functional NMDARs in the cell membrane; and (3) increased NR1 surface
expression, as indicated by cell surface Western blots and
immunofluorescence. Botulinum neurotoxin A or expression of a dominant
negative mutant of synaptosomal associated protein of 25 kDa
molelcular mass (SNAP-25) greatly reduced mGluR1-mediated
potentiation, indicating that receptor trafficking occurs via a
SNAP-25-mediated form of soluble N-ethylmaleimide sensitive
fusion protein attachment protein receptor-dependent exocytosis.
Because group I mGluRs are localized to the perisynaptic region in
juxtaposition to synaptic NMDARs at glutamatergic synapses in the
hippocampus, mGluR-mediated insertion of NMDARs may play a role in
synaptic transmission and plasticity, including long-term potentiation.
Key words:
metabotropic glutamate receptors; NMDA receptors; receptor trafficking; channel gating; protein kinase C; (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylic
acid; ACPD
Copyright © 2001 Society for Neuroscience 0270-6474/01/21166058-11$05.00/0
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