Activation of metabotropic glutamate receptor 1 accelerates NMDA receptor trafficking

Jian Yu Lan, Vytenis A. Skeberdis, Teresa Jover, Xin Zheng, Michael V. L. Bennett, R. Suzanne Zukin

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

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 mGluR1α 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 mGluR1α-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.

Original languageEnglish (US)
Pages (from-to)6058-6068
Number of pages11
JournalJournal of Neuroscience
Volume21
Issue number16
StatePublished - Aug 15 2001

Fingerprint

N-Methyl-D-Aspartate Receptors
Synaptosomal-Associated Protein 25
Metabotropic Glutamate Receptors
Exocytosis
N-Methylaspartate
Synaptic Transmission
Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins
Cell Membrane
Personnel Selection
Type A Botulinum Toxins
Neurotransmitter Receptor
Neuronal Plasticity
Dizocilpine Maleate
Long-Term Potentiation
Xenopus
Synapses
Oocytes
Fluorescent Antibody Technique
Hippocampus
Western Blotting

Keywords

  • (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylic acid
  • ACPD
  • Channel gating
  • Metabotropic glutamate receptors
  • NMDA receptors
  • Protein kinase C
  • Receptor trafficking

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Activation of metabotropic glutamate receptor 1 accelerates NMDA receptor trafficking. / Lan, Jian Yu; Skeberdis, Vytenis A.; Jover, Teresa; Zheng, Xin; Bennett, Michael V. L.; Zukin, R. Suzanne.

In: Journal of Neuroscience, Vol. 21, No. 16, 15.08.2001, p. 6058-6068.

Research output: Contribution to journalArticle

Lan, Jian Yu ; Skeberdis, Vytenis A. ; Jover, Teresa ; Zheng, Xin ; Bennett, Michael V. L. ; Zukin, R. Suzanne. / Activation of metabotropic glutamate receptor 1 accelerates NMDA receptor trafficking. In: Journal of Neuroscience. 2001 ; Vol. 21, No. 16. pp. 6058-6068.
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