Temperature-dependent STIM1 activation induces Ca2+ influx and modulates gene expression

Abstract

Intracellular Ca2+ is essential for diverse cellular functions. Ca2+ entry into many cell types including immune cells is triggered by depleting endoplasmic reticulum (ER) Ca2+, a process termed store-operated Ca2+ entry (SOCE). STIM1 is an ER Ca2+ sensor. Upon Ca2+ store depletion, STIM1 clusters at ER-plasma membrane junctions where it interacts with and gates Ca2+-permeable Orai1 ion channels. Here we show that STIM1 is also activated by temperature. Heating cells caused clustering of STIM1 at temperatures above 35°C without depleting Ca2+ stores, and led to STIM1/Orai1-mediated Ca2+ influx as a heat off-response (response after cooling). Interestingly, the functional coupling of STIM1 and Orai1 is prevented at high temperatures, potentially explaining the heat off-response. Importantly, physiologically-relevant temperature shifts modulates STIM1-dependent gene expression in Jurkat T-cells. Therefore, temperature is an important regulator of STIM1 function.