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Published on: August 22, 2007
Gating and permeation of Orai channels
Isabella Derler1, Rainer Schindl, Reinhard Fritsch
1Institute of Biophysics, University of Linz, A-4040 Linz, Austria. isabella.derler@jku.at
Abstract:
Ca2+ release-activated Ca2+ channels mediate a sustained Ca2+ influx following depletion of endoplasmic reticulum stores. This signalling cascade that triggers T-cell activation or mast cell degranulation involves STIM1, the Ca2+ sensor in the endoplasmic reticulum, and the Ca2+ selective Orai channel in the plasma membrane. This review describes the molecular mechanism (s) governing the STIM1/Orai signalling machinery. Moreover, we provide an overview on additional proteins modulating or interacting with the STIM1/Orai1 system. A structure-function relationship highlights regions within STIM1/Orai proteins contributing to activation, permeation and inactivation of CRAC currents.
Insights
Calcium release-activated calcium channels, involving STIM1 and Orai, control calcium influx crucial for T-cell activation. This review details their molecular mechanisms and interactions.
Area of Science:
- Molecular Biology
- Cell Signaling
- Immunology
Background:
- Calcium release-activated calcium (CRAC) channels are essential for sustained calcium influx after endoplasmic reticulum store depletion.
- This process is critical for cellular functions like T-cell activation and mast cell degranulation.
Purpose of the Study:
- To elucidate the molecular mechanisms of the STIM1/Orai signaling machinery.
- To review additional proteins that modulate or interact with the STIM1/Orai1 system.
- To explore the structure-function relationships of STIM1/Orai proteins in CRAC current regulation.
Main Methods:
- Literature review of STIM1/Orai channel function.
- Analysis of protein interactions and modulators.
- Structure-function analysis of STIM1 and Orai proteins.
Main Results:
- Detailed description of the STIM1/Orai signaling cascade.
- Identification of various proteins interacting with and modulating STIM1/Orai1.
- Correlation of specific protein regions with channel activation, permeation, and inactivation.
Conclusions:
- The STIM1/Orai machinery is a complex system governing calcium influx.
- Understanding these molecular mechanisms and interactions is key to CRAC channel function.
- Structure-function insights provide a basis for further research into channel regulation.
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