NMDA receptor subunits in the postsynaptic density of rat brain: expression and phosphorylation by endogenous protein kinases.
N-methyl-D-aspartate (NMDA) receptors (NRs) play critical roles in diverse synaptic processes in the brain. However, subcellular distribution, spatiotemporal expression and regulation of NR subunits in brain synapses are unknown. We report that NR1 and NR2A-2C subunits are all enriched in the postsynaptic density (PSD), which plays critical roles in trophin-mediated synaptic plasticity. Significant expression of NRs was observed the first two weeks after birth, during synaptogenesis, and in adulthood. Functional diversity of NRs, resulting from heterogeneous composition, was supported by the finding that different NR2 subunits were associated in a region-specific manner with NR1. Phosphorylation of NR1, a key subunit of the NMDA receptor-channel complex, was significantly enhanced by activators of calmodulin (CaM) kinases (CKs) or protein kinase C (PKC), but not by those of PKA. Co-immunoprecipitation studies revealed that NR1 was physically associated with functionally active PKCgamma and the major PSD protein (mPSDp) through noncovalent interactions. Our results suggest that NMDA receptors play roles in postsynaptic mechanisms in a subunit-, composition-, brain region- and developmental-specific manner. Our findings also indicate that the PSD is a coherent functional unit containing protein kinases that potentially regulate NMDA receptor function via phosphorylation.
Suen
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PC
Department of Neuroscience and Cell Biology, UMDNJ/Robert Wood Johnson Medical School and Graduate Program in Physiology and Neurobiology, Rutgers-The State University of New Jersey, 679 Hoes Lane, Piscataway, NJ 08854, USA.
Wu
K
K
Xu
J L
JL
Lin
S Y
SY
Levine
E S
ES
Black
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IB
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000737:chemistry / Q000201:enzymology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006624:Hippocampus / Q000737:chemistry / Q000201:enzymology; D007527:Isoenzymes / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D013569:Synapses / Q000737:chemistry* / Q000502:physiology
D007527:Isoenzymes; D016194:Receptors, N-Methyl-D-Aspartate; D015124:8-Bromo Cyclic Adenosine Monophosphate; C087857:protein kinase C gamma; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C