EF-Hand Proteins and Calcium Sensing

Publisher Summary

This chapter provides an overview of the protein family and its physiological functions, and emphasizes recent developments in the field. The neuronal Ca²⁺-sensor (NCS) proteins have an ever-expanding repertoire of interacting partners that functionally implicate this unique family of Ca²⁺-sensors in an array of diverse cellular pathways. Some of these interactions and the consequences of their dysregulation have been investigated in great detail and have linked NCS proteins to processes with important implications for aspects of human health. EF-hand Ca²⁺ binding proteins fall into two main categories: Ca²⁺ buffers, which act as Ca²⁺ chelators but do not undergo a conformational change; and Ca²⁺ sensors, which, upon Ca²⁺ binding, undergo a conformational change and transfer the signal to other proteins. Members of the neuronal Ca²⁺-sensor (NCS) family include proteins expressed only in the retina (e.g., recoverin) and others expressed mainly in neuronal and neuroendocrine cells, such as the neurocalcins, Visinin-Like Proteins (VILIPs), and NCS-1 (frequenin). The myristoyl group may also be important for protein–protein interactions. A Ca²⁺-myristoyl switch mechanism has been proposed for some members of the family in which the proteins bind membranes in a Ca²⁺-dependent manner via exposure of the myristoyl group upon Ca²⁺ binding. Further in vivo knockout and overexpression studies will reveal more about the roles of the NCS proteins, and clarify their range of physiological functions in the regulation of numerous cellular pathways.