The neuronal calcium sensor family of Ca2+-binding proteins

Ca2+ plays a central role in the function of neurons as the trigger for neu rotransmitter release, and many aspects of neuronal activity, from rapid mo dulation to changes in gene expression, an controlled by Ca2+. These action s of Ca2+ must be mediated by Ca2+-binding proteins, including calmodulin, which is involved in Ca2+ regulation. not only in neurons, but in most othe r cell types. A large number of other EF-hand-containing Ca2+-binding prote ins are known. One family of these, the neuronal calcium sensor (NCS) prote ins, has a restricted expression in retinal photoreceptors or neurons and n euroendocrine cells, suggesting that they have specialized roles in these c ell types. Two members of the family (recoverin and guanylate cyclase-activ ating protein) have established roles in the regulation of phototransductio n. Despite close sequence similarities, the NCS proteins have distinct neur onal distributions, suggesting that they have different functions. Recent w ork has begun to demonstrate the physiological roles of members of this pro tein family. These include roles in the modulation of neurotransmitter rele ase, control of cyclic nucleotide metabolism, biosynthesis of polyphosphoin ositides, regulation of gene expression and in the direct regulation of ion channels. In the present review we describe the known sequences and struct ures of the NCS proteins, information on their interactions with target pro teins and current knowledge about their cellular and physiological function s.