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Updated: Jun 2, 2026

Single-Cell Calcium Imaging for Studying the Activation of Calcium Ion Channels
Published on: December 13, 2024
Temperature-dependent STIM1 activation induces Ca²+ influx and modulates gene expression
Bailong Xiao1, Bertrand Coste, Jayanti Mathur
1Dorris Neuroscience Center, Department of Cell Biology, The Scripps Research Institute, La Jolla, California, USA.
Temperature regulates cellular calcium signaling. STIM1 protein clusters and activates calcium influx in response to cooling, independent of calcium stores, revealing temperature as a key regulator of STIM1 function.
Area of Science:
- Cell Biology
- Molecular Biology
- Physiology
Background:
- Intracellular calcium (Ca2+) is vital for cellular processes, including immune cell function.
- Store-operated Ca2+ entry (SOCE) is a primary mechanism for Ca2+ influx, typically triggered by endoplasmic reticulum (ER) Ca2+ depletion.
- STIM1 acts as an ER Ca2+ sensor, initiating SOCE by interacting with Orai1 channels at ER-plasma membrane junctions.
Purpose of the Study:
- To investigate the role of temperature as a regulator of STIM1 and SOCE.
- To determine if temperature changes can activate STIM1 independently of ER Ca2+ store depletion.
- To explore the impact of temperature shifts on STIM1-Orai1 interactions and downstream cellular responses.
Main Methods:
- Cellular heating and cooling experiments.
- Monitoring STIM1 clustering using fluorescence microscopy.
- Measuring Ca2+ influx through Orai1 channels.
- Analyzing STIM1-dependent gene expression in Jurkat T cells.
Main Results:
- STIM1 clustered at ER-plasma membrane junctions at temperatures above 35 °C, independent of ER Ca2+ store depletion.
- Orai1-mediated Ca2+ influx occurred as a heat off-response after cooling.
- High temperatures inhibited the functional coupling between STIM1 and Orai1.
- Physiologically relevant temperature shifts influenced STIM1-dependent gene expression in Jurkat T cells.
Conclusions:
- Temperature is a significant regulator of STIM1 activation and SOCE.
- The heat off-response is likely due to temperature-dependent inhibition of STIM1-Orai1 coupling.
- Temperature shifts can modulate gene expression in immune cells via STIM1 signaling pathways.
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