Calcium Sensors in Neuronal Function and Dysfunction.

Calcium signaling in neurons as in other cell types can lead to varied changes in cellular function. Neuronal Ca signaling processes have also become adapted to modulate the function of specific pathways over a wide variety of time domains and these can have effects on, for example, axon outgrowth, neuronal survival, and changes in synaptic strength. Ca also plays a key role in synapses as the trigger for fast neurotransmitter release. Given its physiological importance, abnormalities in neuronal Ca signaling potentially underlie many different neurological and neurodegenerative diseases. The mechanisms by which changes in intracellular Ca concentration in neurons can bring about diverse responses is underpinned by the roles of ubiquitous or specialized neuronal Ca sensors. It has been established that synaptotagmins have key functions in neurotransmitter release, and, in addition to calmodulin, other families of EF-hand-containing neuronal Ca sensors, including the neuronal calcium sensor (NCS) and the calcium-binding protein (CaBP) families, play important physiological roles in neuronal Ca signaling. It has become increasingly apparent that these various Ca sensors may also be crucial for aspects of neuronal dysfunction and disease either indirectly or directly as a direct consequence of genetic variation or mutations. An understanding of the molecular basis for the regulation of the targets of the Ca sensors and the physiological roles of each protein in identified neurons may contribute to future approaches to the development of treatments for a variety of human neuronal disorders.