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Life Sciences › Neuroscience › Sensory Systems
The native ORAI channel trio underlies the diversity of Ca2+ signaling events
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Conflicts of Interest
Identified Weaknesses
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Paper Summary
Paperzilla title
ORAI Channel Trio: The Ca2+ Signal Symphony Conductors
This study demonstrates that ORAI2 and ORAI3, often overshadowed by ORAI1, play critical roles in generating regenerative Ca2+ oscillations and fine-tuning receptor-activated Ca2+ signals. These findings suggest that the native CRAC channel functions as a heteromultimer of ORAI isoforms, broadening the sensitivity of cells to diverse agonist concentrations and enabling differential activation of NFAT transcription factors.
Possible Conflicts of Interest
None identified
Identified Weaknesses
Limited generalizability
The reliance on HEK293 cells as a model system limits the generalizability of the findings to other cell types, as the expression and function of ORAI channels can vary.
Overexpression artifacts
The study uses overexpression of ORAI isoforms and concatenated dimers, which may not accurately reflect the native stoichiometry or function of ORAI channels.
Limited physiological relevance
The study focuses on pharmacological activation and does not fully explore the physiological roles of ORAI channels in different cell types.
Rating Explanation
This study provides novel insights into the role of ORAI2 and ORAI3 in shaping Ca2+ signaling and NFAT activation. The use of CRISPR/Cas9 technology to generate ORAI knockout cells is a strength, but the reliance on overexpression systems and pharmacological activation limits the physiological relevance of some findings. Overall, the study represents a valuable contribution to the field of calcium signaling.
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Original Title:
The native ORAI channel trio underlies the diversity of Ca2+ signaling events
File Name:
s41467-020-16232-6.pdf
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File Size:
3.94 MB
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July 14, 2025 at 11:12 AM
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