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Differential roles of NR2A- and NR2B-containing NMDA receptors in Ras-ERK signaling and AMPA receptor trafficking.
Neuron. 2005 Jun 02; 46(5):745-60.N

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.

Authors+Show Affiliations

Kim MJ
The Picower Center for Learning and Memory, RIKEN-MIT Neuroscience Research Center, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Dunah AW
No affiliation info available
Wang YT
No affiliation info available
Sheng M
No affiliation info available

MeSH

AnimalsCell MembraneCells, CulturedExtracellular Signal-Regulated MAP KinasesHippocampusMAP Kinase Signaling SystemN-MethylaspartateProtein TransportRatsReceptors, AMPAReceptors, N-Methyl-D-Aspartateras Proteins

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

15924861

Citation

Kim, Myung Jong, et al. "Differential Roles of NR2A- and NR2B-containing NMDA Receptors in Ras-ERK Signaling and AMPA Receptor Trafficking." Neuron, vol. 46, no. 5, 2005, pp. 745-60.
Kim MJ, Dunah AW, Wang YT, et al. Differential roles of NR2A- and NR2B-containing NMDA receptors in Ras-ERK signaling and AMPA receptor trafficking. Neuron. 2005;46(5):745-60.
Kim, M. J., Dunah, A. W., Wang, Y. T., & Sheng, M. (2005). Differential roles of NR2A- and NR2B-containing NMDA receptors in Ras-ERK signaling and AMPA receptor trafficking. Neuron, 46(5), 745-60.
Kim MJ, et al. Differential Roles of NR2A- and NR2B-containing NMDA Receptors in Ras-ERK Signaling and AMPA Receptor Trafficking. Neuron. 2005 Jun 2;46(5):745-60. PubMed PMID: 15924861.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential roles of NR2A- and NR2B-containing NMDA receptors in Ras-ERK signaling and AMPA receptor trafficking. AU - Kim,Myung Jong, AU - Dunah,Anthone W, AU - Wang,Yu Tian, AU - Sheng,Morgan, PY - 2004/10/12/received PY - 2005/03/17/revised PY - 2005/04/25/accepted PY - 2005/6/1/pubmed PY - 2005/8/2/medline PY - 2005/6/1/entrez SP - 745 EP - 60 JF - Neuron JO - Neuron VL - 46 IS - 5 N2 - 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. SN - 0896-6273 UR - https://www.unboundmedicine.com/medline/citation/15924861/Differential_roles_of_NR2A__and_NR2B_containing_NMDA_receptors_in_Ras_ERK_signaling_and_AMPA_receptor_trafficking_ DB - PRIME DP - Unbound Medicine ER -