ИСТИНА

Intracellular calcium signaling with the participation of Ca2+-sensor proteins is involved in a number of the crucial neuronal functions in health and diseases, among which are reception, neurotransmission, synaptic plasticity, control of neuronal growth, and neuronal survival. In the case of photoreceptor neurons, Ca2+ -sensor proteins are represented by calmodulin and several proteins of the neuronal calcium sensor (NCS) family, including recoverin, guanylyl cyclase activating proteins (GCAPs) and neuronal calcium sensor 1 (NCS1). Retina-specific recoverin and GCAPs are considered as the participants of phototransduction involved in the control of rhodopsin phosphorylation and cGMP synthesis, respectively. In contrast to recoverin and GCAPs, calmodulin and NCS1 are widely distributed in the nervous system and whether these proteins perform specific functions in photoreceptor neurons still remains an open question. In this study, we have attempted (i) to answer this question and (ii) to get insight into the mechanism(s), underlying the specificity of the responses of photoreceptor calcium sensors. To this end, we have used Ca2+ -dependent rhodopsin phosphorylation catalyzing by rhodopsin kinase (G-protein coupled receptor kinase 1, GRK1) as a model of the Ca2+ -sensor-mediated process. It has been found that calmodulin increases the magnitude and Ca2+ -sensitivity of the well-known inhibitory effect of recoverin upon rhodopsin phosphorylation. This result is in agreement with the existence of separate binding sites for recoverin and calmodulin revealed in the GRK1 molecule by biosensor-based approach. Further, it was demonstrated that NCS1 and GCAP2 interact with GRK1 in a Ca2+ -dependent manner. Remarkably, NCS1 acts as inhibitor of the enzyme while GCAP2 apparently does not affect its activity. The roles of the C-terminal segment and the other structural elements of the NCS proteins in the Ca2+ -sensitivity and overall specificity of their action are discussed. This work was supported by the grant #12-04-01045-a from Russian Foundation for Basic Research.