Mechanically gated OSCA/TMEM63 ion channels: From physiological function to structural basis
Siqi Deng1,2, Qinling Qiu1,2, Shangyu Dang1,3
1Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China.
The Journal of Cell Biology
|January 2, 2026
Summary
The OSCA/TMEM63 family, crucial for cellular mechanotransduction, are mechanically gated ion channels. This review explores their roles and proposes a new mechanically gated ion channel superfamily.
Area of Science:
- Biophysics
- Cell Biology
- Molecular Biology
Background:
- The OSCA/TMEM63 family represents the largest known group of mechanically gated ion channels.
- These channels play essential roles in cellular mechanotransduction, responding to mechanical stimuli and osmotic stress.
- Plant OSCAs and animal TMEM63 homologs share functional similarities despite differences in conductance and activation thresholds.
Purpose of the Study:
- To review the physiological and pathological roles of OSCA/TMEM63 proteins.
- To elucidate the molecular mechanisms underlying their function in mechanotransduction.
- To propose a novel mechanically gated ion channel superfamily.
Main Methods:
- Literature review of structural and functional studies.
- Analysis of conserved gating mechanisms.
- Comparative analysis of OSCA/TMEM63 and TMC proteins.
Main Results:
- Structural studies suggest a conserved "force-from-lipid" gating mechanism.
- Membrane tension or curvature directly influences protein conformation and ion flow.
- OSCA/TMEM63 proteins are implicated in various physiological and pathological processes.
Conclusions:
- The OSCA/TMEM63 family is central to cellular mechanotransduction.
- A conserved "force-from-lipid" mechanism governs their gating.
- A new mechanically gated ion channel superfamily, including OSCA/TMEM63 and TMC proteins, is proposed.
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