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Updated: Jul 15, 2026
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Fluorescence-based Measurement of Store-operated Calcium Entry in Live Cells: from Cultured Cancer Cell to Skeletal Muscle Fiber
Published on: February 13, 2012
Some assembly required: constructing the elementary units of store-operated Ca2+ entry
Minnie M Wu1, Riina M Luik, Richard S Lewis
1Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, United States.
Cell Calcium
|May 15, 2007
Summary
Store-operated calcium channels (SOCs) are activated when the endoplasmic reticulum (ER) sensor STIM1 moves to the plasma membrane, interacting with Orai1 to enable calcium entry.
Area of Science:
- Cell Biology
- Molecular Physiology
- Biophysics
Background:
- The mechanism of store-operated calcium channel (SOC) activation following ER calcium depletion remained unclear.
- Previous hypotheses included local ER-plasma membrane interactions or diffusible factors.
- The identification of STIM1 and Orai1 provided tools to investigate this process.
Purpose of the Study:
- To visualize and define the spatiotemporal sequence linking ER calcium store depletion to CRAC channel activation.
- To elucidate the molecular interactions between STIM1 and Orai1 in response to calcium store depletion.
- To understand the structural basis of store-operated calcium entry.
Main Methods:
- Utilized molecular identification of STIM1 (ER calcium sensor) and Orai1 (CRAC channel subunit).
- Observed the dynamic redistribution of STIM1 and Orai1 in response to calcium store depletion.
- Analyzed the proximity of STIM1 and Orai1 at the ER-plasma membrane interface.
Main Results:
- STIM1 translocates from the ER to ER subregions near the plasma membrane (10-25nm) upon store depletion.
- Orai1 accumulates at the plasma membrane directly apposed to STIM1 clusters.
- This co-localization leads to the local activation of CRAC channels and calcium influx.
Conclusions:
- Store-operated calcium entry is mediated by the direct interaction of STIM1 and Orai1 at specialized ER-plasma membrane junctions.
- This mechanism involves a "choreographed" assembly of the sensor and channel, bringing them into proximity for activation.
- This discovery clarifies the elementary units of SOCE and reveals a novel mode of ion channel regulation crucial for calcium signaling specificity.
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