AMPA receptor-dependent clustering of synaptic NMDA receptors is mediated by stargazin and NR2A/B in spinal neurons and hippocampal interneurons

Ruifa Mi, Gek-Ming Sia, Kenneth Rosen, Xiaopei Tang, Abhay Moghekar, John L. Black, Maureen McEnery, Richard L. Huganir, Richard J. O'Brien

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Under standard conditions, cultured ventral spinal neurons cluster AMPA- but not NMDA-type glutamate receptors at excitatory synapses on their dendritic shafts in spite of abundant expression of the ubiquitous NMDA receptor subunit NR1. We demonstrate here that the NMDA receptor subunits NR2A and NR2B are not routinely expressed in cultured spinal neurons and that transfection with NR2A or NR2B reconstitutes the synaptic targeting of NMDA receptors and confers on exogenous application of the immediate early gene product Narp the ability to cluster both AMPA and NMDA receptors. The use of dominant-negative mutants of GluR2 further showed that the synaptic targeting of NMDA receptors is dependent on the presence of synaptic AMPA receptors and that synaptic AMPA and NMDA receptors are linked by Stargazin and a MAGUK protein. This system of AMPA receptor-dependent synaptic NMDA receptor localization was preserved in hippocampal interneurons but reversed in hippocampal pyramidal neurons.

Original languageEnglish (US)
Pages (from-to)335-349
Number of pages15
JournalNeuron
Volume44
Issue number2
DOIs
StatePublished - Oct 14 2004
Externally publishedYes

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Neurotransmitter Receptor
AMPA Receptors
Interneurons
N-Methyl-D-Aspartate Receptors
Cluster Analysis
Neurons
Guanylate Kinases
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Immediate-Early Genes
Pyramidal Cells
Glutamate Receptors
Synapses
Transfection

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

AMPA receptor-dependent clustering of synaptic NMDA receptors is mediated by stargazin and NR2A/B in spinal neurons and hippocampal interneurons. / Mi, Ruifa; Sia, Gek-Ming; Rosen, Kenneth; Tang, Xiaopei; Moghekar, Abhay; Black, John L.; McEnery, Maureen; Huganir, Richard L.; O'Brien, Richard J.

In: Neuron, Vol. 44, No. 2, 14.10.2004, p. 335-349.

Research output: Contribution to journalArticle

Mi, Ruifa ; Sia, Gek-Ming ; Rosen, Kenneth ; Tang, Xiaopei ; Moghekar, Abhay ; Black, John L. ; McEnery, Maureen ; Huganir, Richard L. ; O'Brien, Richard J. / AMPA receptor-dependent clustering of synaptic NMDA receptors is mediated by stargazin and NR2A/B in spinal neurons and hippocampal interneurons. In: Neuron. 2004 ; Vol. 44, No. 2. pp. 335-349.
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AU - Rosen, Kenneth

AU - Tang, Xiaopei

AU - Moghekar, Abhay

AU - Black, John L.

AU - McEnery, Maureen

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AU - O'Brien, Richard J.

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