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Science 287 (5458): 1660-1664

Copyright © 2000 by the American Association for the Advancement of Science

Dual Signaling Regulated by Calcyon, a D1 Dopamine Receptor Interacting Protein

Nelson Lezcano, 1 Ladislav Mrzljak, 2 Steven Eubanks, 1 Robert Levenson, 3 Patricia Goldman-Rakic, 2 Clare Bergson 1*

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.

1 Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA 30912-2300, USA.
2 Section of Neurobiology, Yale School of Medicine, New Haven, CT 06510, USA.
3 Department of Pharmacology, Pennsylvania State College of Medicine, Hershey, PA 17033, USA.
*   To whom correspondence should be addressed. E-mail: cbergson{at}mail.mcg.edu


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