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12:30
Monitoring ER/SR Calcium Release with the Targeted Ca2+ Sensor CatchER+
Published on: May 19, 2017
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STIM proteins: dynamic calcium signal transducers.
Jonathan Soboloff1, Brad S Rothberg, Muniswamy Madesh
1Department of Biochemistry, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, Pennsylvania 19140, USA.
Nature Reviews. Molecular Cell Biology
|August 24, 2012
Summary
Stromal interaction molecule (STIM) proteins sense endoplasmic reticulum (ER) calcium (Ca2+) levels. Activated STIM proteins then regulate Orai channels at ER-plasma membrane junctions to control cellular Ca2+ signals.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Stromal interaction molecule (STIM) proteins are key regulators of cellular calcium (Ca2+) signaling.
- STIM proteins reside in the endoplasmic reticulum (ER) membrane, sensing luminal Ca2+ levels.
- Dysregulation of cellular Ca2+ homeostasis is implicated in various diseases.
Purpose of the Study:
- To elucidate the mechanism by which STIM proteins sense and respond to ER Ca2+.
- To investigate the role of STIM proteins in the formation and function of ER-plasma membrane junctions.
- To identify novel regulators and interacting partners of STIM proteins.
Main Methods:
- Confocal microscopy to visualize STIM protein translocation.
- Patch-clamp electrophysiology to measure Orai channel activity.
- Biochemical assays to identify STIM protein interactors.
Main Results:
- STIM proteins undergo conformational changes and translocate to ER-plasma membrane junctions upon ER Ca2+ depletion.
- STIM proteins directly bind and activate Orai channels, forming a crucial signaling complex.
- Novel regulatory proteins and alternative STIM targets have been identified, expanding the known STIM interactome.
Conclusions:
- STIM proteins act as critical sensors and effectors in cellular Ca2+ signaling.
- The STIM-Orai axis is essential for maintaining cellular Ca2+ homeostasis.
- Further research into STIM-protein interactions may reveal new therapeutic targets for Ca2+-related disorders.
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