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 t hat mediate the resultant signal amplification have not been defined. Here a 24-kilodalton single transmembrane protein, designated calcyon, we functi onally characterize that interacts with the D1 dopamine receptor. Calcyon L ocalizes to dendritic spines of D1 receptor-expressing pyramidal cells in p refrontal cortex. These studies delineate a mechanism of G(q)- and G(s)-cou pled heterotrimeric CTP-binding protein-coupled receptor cross talk by whic h D1 receptors can shift effector coupling to stimulate robust intracellula r calcium (Ca-i(2+)) release as a result of interaction with calcyon. The r ole of calcyon in potentiating Ca2+-dependent signaling should provide insi ght into the D1 receptor-modulated cognitive functions of prefrontal cortex .