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Physiological Functions of CRAC Channels
Scott M Emrich1, Ryan E Yoast1, Mohamed Trebak1,2
1Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA;
Annual Review of Physiology
|October 12, 2021
Summary
Store-operated calcium entry (SOCE) is a vital signaling pathway. Recent studies reveal CRAC channel composition and physiological roles in immunity, muscle, and nerve systems, offering insights from mouse models and human diseases.
Area of Science:
- Cellular Biology
- Physiology
- Molecular Biology
Background:
- Store-operated calcium entry (SOCE) is a fundamental, evolutionarily conserved calcium signaling pathway.
- SOCE is initiated by the depletion of endoplasmic reticulum (ER) calcium stores, activating inositol 1,4,5-trisphosphate receptors.
- The process involves STIM proteins sensing ER calcium levels and interacting with Orai proteins to form calcium release-activated calcium (CRAC) channels.
Purpose of the Study:
- To review recent findings on the molecular composition of native CRAC channels.
- To elucidate the physiological functions of SOCE in various mammalian systems.
- To connect insights from transgenic mouse models and human diseases to CRAC channel activity.
Main Methods:
- Analysis of studies involving STIM and Orai tissue-specific knockout mice.
- Examination of human gain- and loss-of-function mutations affecting CRAC channel activity.
- Synthesis of recent research on native CRAC channel composition and function.
Main Results:
- CRAC channels are highly calcium-selective and composed of Orai proteins.
- STIM proteins are essential for CRAC channel activation upon ER store depletion.
- SOCE plays critical roles in immune cell function, muscle contraction, secretory processes, and neuronal signaling.
Conclusions:
- Understanding CRAC channel composition and function is crucial for comprehending diverse physiological processes.
- Transgenic mouse models and human genetic studies provide valuable insights into SOCE's role in health and disease.
- Further research on CRAC channels can illuminate therapeutic strategies for diseases linked to calcium dysregulation.
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