Temperature-dependent STIM1 activation induces Ca2+ influx and modulates gene expression
Open Access
- 17 April 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Chemical Biology
- Vol. 7 (6), 351-358
- https://doi.org/10.1038/nchembio.558
Abstract
Heat causes oligomerization and targeting of the ER-based calcium sensor STIM1 to ER–plasma membrane junctions but prevents the functional coupling between STIM1 and the calcium-permeable Orai1 ion channel, resulting in a unique heat off-response of calcium entry. 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 Orai1-mediated Ca2+ 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.Keywords
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