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How many Orai's does it take to make a CRAC channel?
Jill L Thompson1, Trevor J Shuttleworth
1Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Scientific Reports
|June 8, 2013
Summary
Calcium Release-Activated Calcium (CRAC) channels are crucial for cellular calcium entry. This study reveals that tetrameric Orai1 channels exhibit CRAC channel properties, unlike hexameric channels.
Area of Science:
- Molecular Biology
- Cell Physiology
- Ion Channel Function
Background:
- Calcium Release-Activated Calcium (CRAC) channels mediate store-operated calcium entry.
- CRAC channels are vital for T-cell activation and mast cell inflammatory responses.
- Orai proteins form CRAC channels, with previous models suggesting a tetrameric structure.
Purpose of the Study:
- To investigate the oligomeric state of human Orai1 channels responsible for CRAC channel function.
- To compare the biophysical properties of tetrameric versus hexameric Orai1 channel constructs.
Main Methods:
- Expression of concatenated hexameric and tetrameric human Orai1 channels in HEK293 cells.
- Biophysical characterization of ion channel conductance and selectivity.
- Comparison with endogenous CRAC channel properties.
Main Results:
- Tetrameric Orai1 channels displayed highly calcium-selective conductance, consistent with endogenous CRAC channels.
- Hexameric Orai1 constructs formed non-selective cation channels.
- Oligomeric state significantly impacts Orai1 channel function and ion selectivity.
Conclusions:
- The tetrameric assembly of Orai1 is essential for forming functional, calcium-selective CRAC channels.
- The hexameric structure does not replicate the selective ion permeability of native CRAC channels.
- Findings clarify the structural basis of CRAC channel selectivity.
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