Role of STIM2 in cell function and physiopathology

Abstract

An endoplasmic reticulum (ER)–resident protein that regulates cytosolic and ER free-Ca²⁺ concentration by induction of store–operated calcium entry. That is the original definition of STIM2 and its function. While its activity strongly depends on the amount of calcium stored in the ER, its function goes further to intracellular signalling and gene expression. Initially undercovered by the prominent function of STIM1, STIM2 became to be vital in mice, gradually emerging as an important player in the nervous system, and cooperating with STIM1 in the immune system. STIM2 has also been proposed as a relevant player in pathological conditions related to ageing, Alzheimer and Huntington's diseases, autoimmune disorders and cancer. The discovery of additional functions, together with new splicing forms with opposite roles, clarified existing controversies about STIM2 function in SOCE. Being essential for life, but apparently not for development, new available data demonstrated a complex and still intriguing behaviour that this review summarizes, updating the current knowledge about STIM2 function.

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