This Research Topic is part of the Molecular Components of Store-Operated Calcium Entry in Health and Disease series:
Molecular Components of Store-Operated Calcium Entry in Health and Disease The Store-Operated Ca2+ Entry (SOCE), a specific and ubiquitous type of Ca2+ influx mechanism, is an important element of Ca2+ homeostasis in both excitable and non-excitable cells, with important physiological implications. This pathway is activated by depletion of Ca2+ within the lumen of endoplasmic reticulum (ER) and initiated by ER Ca2+ sensors, which include Stromal Interacting Molecule (STIM) proteins - STIM1 and STIM2. Emptying ER Ca2+ stores induces oligomerization of STIM proteins and migration of the oligomers towards ER regions juxtaposed to the plasma membrane (PM), where they form complexes with Store-dependent Ca2+ Channels (SOCC). There are two types of SOCC pore-forming subunits in PM regulated by STIMs including Orai (Orai1, Orai2, Orai3) and Transient Receptor Potential Canonical (TRPC) proteins.
However, replenishment of intracellular Ca2+ stores is not the only function of these proteins. It has recently been found that STIM proteins, Orai and TRP channels regulate Ca2+ influx, which performs signaling functions and modulates several physiological processes such as cell migration, platelet function, muscle contraction, cell proliferation, neuronal activity, spinal morphogenesis and synaptic transmission, etc. Over the past few years, an increasing number of disorders (cardiovascular diseases, muscle diseases, immune disorders and carcinogenesis) and neurodegenerative diseases (stroke, cerebral ischemia, Alzheimer's (AD), Huntington's and Parkinson's diseases) have been associated with altered functions of SOCE compounds. For example, STIM2 protein levels were significantly reduced in hippocampal neurons in a mouse model of familial AD, and in cortical samples from sporadic AD patients. Additionally, disturbances in the signaling pathway that involves STIM led to the loss of mushroom spines, severe brain lesions, and deficits in spatial memory (symptoms observed in neurodegenerative diseases).
Although significant data has been accumulated in recent years, many aspects associated with Orai - a highly Ca2+ selective ion channel, non-selective TRPC channels and ER Ca2+ sensors - STIM proteins are still elusive. Thus, this Research Topic will discuss the current state of knowledge on the mechanism of action of these proteins, cellular functions, relevance to cellular signaling, partner proteins, participation in physiological processes and diseases and their therapeutic potential. We welcome original research, up-to-date short communication (mini review) and review articles on any of these aspects.