RETRACTED: Dual signaling regulated by calcyon, a D1 dopamine receptor interacting protein.
The synergistic response of cells to the stimulation of multiple receptors has been ascribed to receptor cross talk; however, the specific molecules that mediate the resultant signal amplification have not been defined. Here a 24-kilodalton single transmembrane protein, designated calcyon, we functionally characterize that interacts with the D1 dopamine receptor. Calcyon localizes to dendritic spines of D1 receptor-expressing pyramidal cells in prefrontal cortex. These studies delineate a mechanism of Gq- and Gs-coupled heterotrimeric GTP-binding protein-coupled receptor cross talk by which D1 receptors can shift effector coupling to stimulate robust intracellular calcium (Ca2+i) release as a result of interaction with calcyon. The role of calcyon in potentiating Ca2+-dependent signaling should provide insight into the D1 receptor-modulated cognitive functions of prefrontal cortex.
Lezcano
N
N
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA 30912-2300, USA.
Mrzljak
L
L
Eubanks
S
S
Levenson
R
R
Goldman-Rakic
P
P
Bergson
C
C
D000595:Amino Acid Sequence; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D003712:Dendrites / Q000737:chemistry / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D005260:Female; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008253:Macaca mulatta; D008565:Membrane Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D017397:Prefrontal Cortex / Q000166:cytology / Q000378:metabolism*; D017966:Pyramidal Cells / Q000737:chemistry / Q000378:metabolism*; D011817:Rabbits; D020239:Receptor Cross-Talk; D017447:Receptors, Dopamine D1 / Q000032:analysis / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D020798:Two-Hybrid System Techniques
D001552:Benzazepines; D018491:Dopamine Agonists; D008565:Membrane Proteins; D017447:Receptors, Dopamine D1; D017981:Receptors, Neurotransmitter; D011993:Recombinant Fusion Proteins; C405464:calcyon; C067113:SK&F 81297; D000242:Cyclic AMP; D020962:Heterotrimeric GTP-Binding Proteins; D002118:Calcium