Alternative forms of the store-operated calcium entry mediators, STIM1 and Orai1

Activation of phospholipase C results in release of intracellular Ca(2+) and activation of Ca(2+) entry. Plasma membrane Ca(2+) entry most commonly is signaled by the depletion of intracellular Ca(2+) stores, a mechanism referred to as capacitative calcium entry or store-operated calcium entry (SOCE). The major players in the SOCE pathway are a Ca(2+) sensor protein, STIM1, and a channel subunit, Orai1. STIM1 activates Orai channels by a mechanism that depends upon its colocalization with Orai at endoplasmic reticulum-plasma membrane junctions. Signaling proteins often occur in multiple forms with distinct properties and/or functions. Such forms arise by a number of mechanisms, including covalent modification, alternative splicing, and alternative translation initiation. This chapter summarizes and discusses recent work revealing alternative forms of STIM1 and Orai1, and the physiological consequences of these modified proteins.