title: Temperature-dependent STIM1 activation induces Ca²+ influx and modulates gene expression.
abstract: Intracellular Ca(2+) is essential for diverse cellular functions. Ca(2+) entry into many cell types including immune cells is triggered by depleting endoplasmic reticulum (ER) Ca(2+), a process termed store-operated Ca(2+) entry (SOCE). STIM1 is an ER Ca(2+) sensor. Upon Ca(2+) store depletion, STIM1 clusters at ER-plasma membrane junctions where it interacts with and gates Ca(2+)-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 Ca(2+) stores and led to Orai1-mediated Ca(2+) influx as a heat off-response (response after cooling). Notably, the functional coupling of STIM1 and Orai1 is prevented at high temperatures, potentially explaining the heat off-response. Additionally, physiologically relevant temperature shifts modulate STIM1-dependent gene expression in Jurkat T cells. Therefore, temperature is an important regulator of STIM1 function.
authors.affiliation: Dorris Neuroscience Center, Department of Cell Biology, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Bailong
authors.initials: B
authors.lastname: Xiao
authors.forename: Bertrand
authors.initials: B
authors.lastname: Coste
authors.forename: Jayanti
authors.initials: J
authors.lastname: Mathur
authors.forename: Ardem
authors.initials: A
authors.lastname: Patapoutian
mesh_terms: D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D004721:Endoplasmic Reticulum; D005786:Gene Expression Regulation; D006358:Hot Temperature; D006801:Humans; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D000071740:ORAI1 Protein; D000071737:Stromal Interaction Molecule 1; D013696:Temperature
chemical_list: D015220:Calcium Channels; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D002118:Calcium