Mechanism of STIM activation

Store-operated calcium entry (SOCE) through Orai ion channels is an intracellular signaling pathway that is initiated by ligand-induced depletion of calcium from the endoplasmic reticulum (ER) store. The molecular link between SOCE and ER store depletion is thereby provided by a distinct class of single pass ER transmembrane proteins known as stromal interaction molecules (STIM). STIM proteins are equipped with a precise N-terminal calcium sensing domain that enables them to react to changes of the ER luminal calcium concentration. Additionally, a C-terminal coiled-coil domain permits relaying of signals to Orai ion channels via direct physical interaction. In this review, we provide a brief introduction to STIM proteins with a focus on structure and function and give an overview of recent developments in the field of STIM research.