Nervous system pathophysiological perspective of neuronal store-operated Ca2+ signaling

Abstract

Calcium (Ca2+), as a ubiquitous second messenger, performs significant physiological tasks in regulating a plethora of neuronal functions including neurosecretion, exocytosis, neuronal growth/differentiation, and the development and maintenance of neural circuits. An important regulatory aspect of neuronal Ca2+ homeostasis is store-operated Ca2+ entry (SOCE), which, in recent years, has gained much attention for influencing a variety of nerve cell responses. Essentially, activation of SOCE ensues following the activation of the plasma membrane (PM) store-operated Ca2+ channels (SOCC) triggered by the depletion of endoplasmic reticulum (ER) Ca2+ stores. In addition to the TRP (Transient receptor potential) family of ion channels, the recently identified Orai and STIM (stromal interacting molecule) proteins have been baptized as key molecular components of SOCE. Functional significance of the TRP channels in neurons has been elaborately studied however, information on Orai and STIM components of SOCE, although seems imminent, is currently limited. Importantly, perturbations in SOCE have been implicated in a spectrum of neuropathological conditions. Hence, understanding the precise involvement of SOCC in neurodegeneration would presumably unveil avenues for plausible therapeutic interventions. We thus review the role of SOCE-regulated neuronal Ca2+ signaling in select neurodegenerative conditions.