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Differential Roles of NR2A- and NR2B-Containing NMDA Receptors in Ras-ERK Signaling and AMPA Receptor Trafficking

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Kim, Myung Jong, Dunah, Anthone W., Wang, Yu Tian, Sheng, Morgan·2005·Neuron

DOI 10.1016/j.neuron.2005.04.031

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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.

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Glutamate Receptors: NMDA and Delta Receptors
Yuzaki, M. (2009) · Springer eBooks · doi:10.1007/978-0-387-30370-3_16
Efeitos do Antagonismo dos Receptores de Peptídeos Semelhantes à Bombesina, o GRPR e o NMBR, durante o Desenvolvimento em Ratos
Torres, J. P. (2011) · Americanae (AECID Library)

Authors: Kim, M. J., Dunah, A. W., Wang, Y. T., & Sheng, M.
Affiliations: Howard Hughes Medical Institute (US)
University of British Columbia Hospital (CA)
Corresponding author: Sheng, Morgan
ORCID: Kim, Myung Jong
Wang, Yu Tian
Sheng, Morgan
Venue: Neuron
Publisher: Elsevier BV
Published: 2005-06
Volume: 46
Issue: 5
Pages: 745-760
ISSN: 0896-6273 (ISSN-L)
DOI: 10.1016/j.neuron.2005.04.031
OpenAlex: W2032596004
Cited by: 494
References: 49
Citations by year: 2026: 5 · 2025: 13 · 2024: 12 · 2023: 13 · 2022: 8 · 2021: 10 · 2020: 11 · 2019: 23 · 2018: 25 · 2017: 29 · 2016: 21 · 2015: 21 · 2014: 24 · 2013: 18 · 2012: 32
FWCI: 13.50
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2968 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Neuron (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords: NMDA receptor, NR2A, NR2B, AMPA receptor trafficking, GluR1, Ras/ERK signaling, SynGAP, synaptic plasticity, synaptic transmission, receptor subunit composition
MeSH terms: Animals, Cell Membrane, Cells, Cultured, Hippocampus, Receptors, N-Methyl-D-Aspartate, N-Methylaspartate, Receptors, AMPA, ras Proteins, MAP Kinase Signaling System, Protein Transport, Extracellular Signal-Regulated MAP Kinases, Rats

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Differential Roles of NR2A- and NR2B-Containing NMDA Receptors in Ras-ERK Signaling and AMPA Receptor Trafficking

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