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PMID: 11466426 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Dopamine D1 receptor-dependent trafficking of striatal NMDA glutamate receptors to the postsynaptic membrane.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 21 ·No. 15 ·2001-08-01 ·Pages 5546-58

Dunah AW, Standaert DG

Abstract

Recent work has shown substantial alterations in NMDA receptor subunit expression, assembly, and phosphorylation in the dopamine-depleted striatum of a rodent 6-hydroxydopamine model of Parkinson's disease. These modifications are hypothesized to result from the trafficking of NMDA receptors between subcellular compartments. Here we show that in rat striatal tissues the NR2A and NR2B subunits in the synaptosomal membrane, and not those in the light membrane and synaptic vesicle-enriched compartments, are tyrosine phosphorylated. The dopamine D1 receptor agonist SKF-82958 produces (1) an increase in NR1, NR2A, and NR2B proteins in the synaptosomal membrane fraction; (2) a decrease in NR1, NR2A, and NR2B proteins in the light membrane and synaptic vesicle-enriched fractions; and (3) an increase in the tyrosine phosphorylation of NR2A and NR2B in the synaptosomal membrane compartment. The protein phosphatase inhibitor pervanadate reproduces the alterations in subcellular distribution and phosphorylation, whereas the effects of the dopamine D1 receptor agonist are blocked by genistein, a protein tyrosine kinase inhibitor. Dopamine D1 receptor agonist treatment does not change the subcellular distribution of the AMPA receptor subunits GluR1 or GluR2/3 in the striatum and has no effect on cortical or cerebellar NMDA receptor subunits. These data reveal a rapid dopamine D1 receptor- and tyrosine kinase-dependent trafficking of striatal NMDA receptors between intracellular and postsynaptic sites. The subcellular trafficking of striatal NMDA receptors may play a significant role both in the pathogenesis of Parkinson's disease and in the development of adverse effects of chronic dopaminergic therapy in parkinsonian patients.

MeSH Terms
Animals Cell Compartmentation/drug effects,physiology Corpus Striatum/chemistry,metabolism Dopamine Agonists/pharmacology Enzyme Inhibitors/pharmacology In Vitro Techniques Male Phosphorylation/drug effects Protein Transport/physiology Protein-Tyrosine Kinases/antagonists & inhibitors,metabolism Rats Receptors, AMPA/chemistry,metabolism Receptors, Dopamine D1/agonists,metabolism Receptors, N-Methyl-D-Aspartate/chemistry,metabolism Subcellular Fractions/chemistry,drug effects,metabolism Synaptic Membranes/chemistry,metabolism Synaptic Vesicles/chemistry,metabolism Synaptosomes/chemistry,metabolism
Chemicals
Dopamine Agonists Enzyme Inhibitors NR1 NMDA receptor NR2A NMDA receptor NR2B NMDA receptor Receptors, AMPA Receptors, Dopamine D1 Receptors, N-Methyl-D-Aspartate glutamate receptor ionotropic, AMPA 3 Protein-Tyrosine Kinases glutamate receptor ionotropic, AMPA 2 glutamate receptor ionotropic, AMPA 1
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Dunah A W
Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
Standaert D G
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2001-08-01
Pages
5546-58
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6762635
Subset
IM
Grants
NINDS NIH HHS · NS34361 · United States
External Links
PubMed source PMC Full Text View journal details
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