Ca2+ signaling and STIM1

Abstract

An increase in the intracellular calcium ion concentration ([Ca(2+)]) impacts a diverse range of cell functions, including adhesion, motility, gene expression and proliferation. Elevation of intracellular calcium ion (Ca(2+)) regulates various cellular events after the stimulation of cells. Initial increase in Ca(2+) comes from the endoplasmic reticulum (ER), intracellular storage space. However, the continuous influx of extracellular Ca(2+) is required to maintain the increased level of Ca(2+) inside cells. Store-operated Ca(2+) entry (SOCE) manages this process, and STIM1, a newly discovered molecule, has a unique and essential role in SOCE. STIM1 can sense the exhaustion of Ca(2+) in the ER, and activate the SOC channel in the plasma membrane, leading to the continuous influx of extracellular Ca(2+). STIM1 senses the status of the intracellular Ca(2+) stores via a luminal N-terminal Ca(2+)-binding EF-hand domain. Dissociation of Ca(2+) from this domain induces the clustering of STIM1 to regions of the ER that lie close to the plasma membrane, where it regulates the activity of the store-operated Ca(2+) channels/entry (calcium-release-activated calcium channels/entry). In this review, we summarize the mechanism by which STIM1 regulates SOCE, and also its role in the control of mast cell functions and allergic responses.