Receptors for dopamine and somatostatin: formation of hetero-oligomers with enhanced functional activity.
Somatostatin and dopamine are two major neurotransmitter systems that share a number of structural and functional characteristics. Somatostatin receptors and dopamine receptors are colocalized in neuronal subgroups, and somatostatin is involved in modulating dopamine-mediated control of motor activity. However, the molecular basis for such interaction between the two systems is unclear. Here, we show that dopamine receptor D2R and somatostatin receptor SSTR5 interact physically through hetero-oligomerization to create a novel receptor with enhanced functional activity. Our results provide evidence that receptors from different G protein (heterotrimeric guanine nucleotide binding protein)-coupled receptor families interact through oligomerization. Such direct intramembrane association defines a new level of molecular crosstalk between related G protein-coupled receptor subfamilies.
Rocheville
M
M
Fraser Laboratories, Department of Medicine, McGill University and Royal Victoria Hospital, Montreal, Quebec H3A 1A1, Canada.
Lange
D C
DC
Kumar
U
U
Patel
S C
SC
Patel
R C
RC
Patel
Y C
YC
D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D019281:Dimerization; D065127:Dopamine D2 Receptor Antagonists; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008297:Male; D009474:Neurons / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D020239:Receptor Cross-Talk; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D017481:Receptors, Somatostatin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism / Q000494:pharmacology; D013134:Spiperone / Q000494:pharmacology; D013469:Sulpiride / Q000494:pharmacology; D014162:Transfection
D065127:Dopamine D2 Receptor Antagonists; D008024:Ligands; D017448:Receptors, Dopamine D2; D017481:Receptors, Somatostatin; D005576:Colforsin; D019257:Quinpirole; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D013134:Spiperone; D013004:Somatostatin; D013469:Sulpiride; C094573:somatostatin receptor 5; D000242:Cyclic AMP; D020962:Heterotrimeric GTP-Binding Proteins