Differential roles of NR2A- and NR2B-containing NMDA receptors in Ras-ERK signaling and AMPA receptor trafficking

Jong Kim Myung, Anthone W. Dunah, Tian Wang Yu, Morgan Sheng*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

367 Scopus citations

Abstract

NMDA receptors (NMDARs) control bidirectional synaptic plasticity by regulating postsynaptic AMPA receptors (AMPARs). Here we show that NMDAR activation can have differential effects on AMPAR trafficking, depending on the subunit composition of NMDARs. In mature cultured neurons, NR2A-NMDARs promote, whereas NR2B-NMDARs inhibit, the surface expression of GluR1, primarily by regulating its surface insertion. In mature neurons, NR2B is coupled to inhibition rather than activation of the Ras-ERK pathway, which drives surface delivery of GluR1. Moreover, the synaptic Ras GTPase activating protein (GAP) SynGAP is selectively associated with NR2B-NMDARs in brain and is required for inhibition of NMDAR-dependent ERK activation. Preferential coupling of NR2B to SynGAP could explain the subtype-specific function of NR2B-NMDARs in inhibition of Ras-ERK, removal of synaptic AMPARs, and weakening of synaptic transmission.

Original languageEnglish (US)
Pages (from-to)745-760
Number of pages16
JournalNeuron
Volume46
Issue number5
DOIs
StatePublished - Jun 2 2005

ASJC Scopus subject areas

  • Neuroscience(all)

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