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

Abstract

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 G _q - and G _s -coupled heterotrimeric GTP–binding protein–coupled receptor cross talk by which D1 receptors can shift effector coupling to stimulate robust intracellular calcium (Ca ²⁺ _i ) release as a result of interaction with calcyon. The role of calcyon in potentiating Ca ²⁺ -dependent signaling should provide insight into the D1 receptor–modulated cognitive functions of prefrontal cortex.