Regulation of Calcium Signaling by STIM1 and ORAI1

Abstract

STIM1 and ORAI1 proteins are regulators of intracellular Ca 2+ mobilization. This Ca 2+ mobilization is essential to shape Ca 2+ signaling in eukaryotic cells. STIM1 is a transmembrane protein located at the endoplasmic reticulum, where it acts as an intraluminal Ca 2+ sensor. The transient drop of intraluminal Ca 2+ concentration triggers STIM1 activation, which relocates to plasma membrane-endoplasmic reticulum junctions to bind and acti- vate ORAI1, a plasma membrane Ca 2+ channel. Thus, the Ca 2+ influx pathway mediated by STIM1/ORAI1 is termed store-operated Ca 2+ entry (SOCE). STIM and ORAI proteins are also involved in non-SOCE Ca 2+ influx pathways, as we discuss here. In this chapter, we review the current knowledge regarding the role of SOCE, STIM1, and ORAI1 in cell signaling, with special focus on the modulation of the activity of kinases, phosphatases, and transcription factors that are strongly influenced by the extracellular Ca 2+ influx mediated by these regulators. Palmitate induces ER calcium