IDENTIFICATION OF A NEURONAL CALCIUM SENSOR (NCS-1) POSSIBLY INVOLVEDIN THE REGULATION OF RECEPTOR PHOSPHORYLATION

Persistent stimulation of G protein-coupled receptors by agonists lead s rapidly to reduced responses, a phenomenon described as desensitizat ion. It involves primarily the phosphorylation of receptor sites by sp ecific kinases of the G protein-coupled receptor kinase (GRK) family. The beta-adrenergic receptor kinase 1 (GRK2) desensitizes agonist-acti vated beta(2)-adrenergic receptors, whereas rhodopsin kinase (GRK1) ph osphorylates and inactivates photon-activated rhodopsin. Little is kno wn about the role of calcium in desensitization. Here we report the ch aracterization of a novel neuronal calcium sensor (NCS) named NCS-1 po ssibly involved in the regulation of receptor phosphorylation. NCS-1 i s a new member of the EF-hand superfamily, which includes calmodulin, troponin C, parvalbumin, and recoverins. By Northern analysis and in s itu hybridization, we discovered that NCS-1 is specifically expressed in the central and peripheral nervous systems. Chick NCS-1 has 72% of amino acid identity with Drosophila frequenin, a protein found in the nervous system and at the motor nerve terminals of neuromuscular junct ions. By analogy with the reported function for two other members of t he NCS family, we discuss whether G protein-coupled receptors or GRKs are the targets of neuronal calcium sensors.