Lezcano N, Mrzljak L, Eubanks S, Levenson R, Goldman-Rakic P, Bergson C
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA 30912-2300, USA.
Science. 2000 Mar 3;287(5458):1660-4. doi: 10.1126/science.287.5458.1660.
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.
细胞对多种受体刺激的协同反应被归因于受体间的相互作用；然而，介导信号放大的具体分子尚未明确。在此，我们对一种与D1多巴胺受体相互作用的24千道尔顿单跨膜蛋白（命名为钙调蛋白）进行了功能表征。钙调蛋白定位于前额叶皮质中表达D1受体的锥体细胞的树突棘。这些研究描绘了一种Gq和Gs偶联的异三聚体GTP结合蛋白偶联受体相互作用的机制，通过该机制，D1受体可因与钙调蛋白相互作用而改变效应器偶联，从而刺激强大的细胞内钙（Ca2+i）释放。钙调蛋白在增强钙依赖性信号传导中的作用应为深入了解前额叶皮质的D1受体调节的认知功能提供线索。
