AMPA receptor-dependent clustering of synaptic NMDA receptors is mediated by Stargazin and NR2A/B in spinal neurons and hippocampal interneurons.
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.
Department of Neurology, Johns Hopkins University, Baltimore, MD 21205, USA.
Ruifa
R
Mi
Gek-Ming
GM
Sia
Kenneth
K
Rosen
Xiaopei
X
Tang
Abhay
A
Moghekar
John L
JL
Black
Maureen
M
McEnery
Richard L
RL
Huganir
Richard J
RJ
O'Brien
D000818:Animals; D015152:Blotting, Northern; D002097:C-Reactive Protein / Q000502:physiology; D015220:Calcium Channels / Q000502:physiology*; D002478:Cells, Cultured; D051528:Guanylate Kinases; D006624:Hippocampus / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D009419:Nerve Tissue Proteins / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D009703:Nucleoside-Phosphate Kinase / Q000502:physiology; D021122:Protein Subunits / Q000502:physiology; D051381:Rats; D018091:Receptors, AMPA / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D014162:Transfection; D000099153:Pentraxins
D002097:C-Reactive Protein; D015220:Calcium Channels; D051528:Guanylate Kinases; D009419:Nerve Tissue Proteins; D009703:Nucleoside-Phosphate Kinase; D021122:Protein Subunits; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D000099153:Pentraxins; C491911:Cacng2 protein, rat