Related Experiment Video
Updated: Jun 22, 2026

Single-Cell Calcium Imaging for Studying the Activation of Calcium Ion Channels
Published on: December 13, 2024
STIM and Orai: dynamic intermembrane coupling to control cellular calcium signals
Xiaoxiang Deng1, Youjun Wang, Yandong Zhou
1Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Calcium (Ca2+) signaling relies on store release and external entry, coordinated by STIM and Orai proteins. This study reveals new insights into how these proteins interact at the ER-PM junction to control Ca2+ signals.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Calcium (Ca2+) signals regulate numerous cellular functions.
- These signals involve both intracellular Ca2+ store release and extracellular Ca2+ influx.
- Coordination between these Ca2+ sources is crucial for cellular processes.
Purpose of the Study:
- To elucidate the mechanism of intermembrane coupling between STIM and Orai proteins.
- To describe the functional roles of STIM and Orai in controlling Ca2+ signals.
- To provide a new understanding of the proteins involved in Ca2+ signal regulation.
Main Methods:
- Investigated the redistribution of STIM proteins from the endoplasmic reticulum (ER) to ER-plasma membrane (PM) junctions.
- Characterized the migration and tethering of Orai proteins at these junctions.
- Analyzed the function of STIM-Orai complexes in mediating Ca2+ entry.
Main Results:
- STIM proteins act as ER luminal Ca2+ sensors, forming discrete junctional domains.
- Orai proteins, PM Ca2+ channels, are recruited and tethered by STIM at ER-PM junctions.
- This STIM-Orai interaction facilitates highly selective Ca2+ entry, controlling cellular Ca2+ signals.
Conclusions:
- STIM and Orai proteins form a critical intermembrane signaling complex.
- This complex dynamically coordinates Ca2+ store release and entry.
- Understanding STIM-Orai function offers new insights into Ca2+ signal regulation.
Related Concept Videos
Feedback Regulation of Calcium Concentration
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Calmodulin-dependent Signaling
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
Amplifying Signals via Second Messengers
Smooth Muscle Contraction
The onset of contraction is triggered by an increase in calcium ions within the sarcoplasm, similar to the process in striated muscle. However, smooth muscles have a relatively smaller reservoir of the sarcoplasmic...
What are Second Messengers?
Excitation-Contraction Coupling in Skeletal Muscles
When an action potential...

