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Discoveries in structure and physiology of mechanically activated ion channels

Abstract

The ability to sense physical forces is conserved across all organisms. Cells convert mechanical stimuli into electrical or chemical signals via mechanically activated ion channels. In recent years, the identification of new families of mechanosensitive ion channels—such as PIEZO and OSCA/TMEM63 channels—along with surprising insights into well-studied mechanosensitive channels have driven further developments in the mechanotransduction field. Several well-characterized mechanosensory roles such as touch, blood-pressure sensing and hearing are now linked with primary mechanotransducers. Unanticipated roles of mechanical force sensing continue to be uncovered. Furthermore, high-resolution structures representative of nearly every family of mechanically activated channel described so far have underscored their diversity while advancing our understanding of the biophysical mechanisms of pressure sensing. Here we summarize recent discoveries in the physiology and structures of known mechanically activated ion channel families and discuss their implications for understanding the mechanisms of mechanical force sensing.

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Fig. 1: Structures of mechanically activated ion channels.
Fig. 2: Mechanistic models of mechanically activated ion channel gating.
Fig. 3: Lipids observed in structures of mechanosensitive ion channels.
Fig. 4: The MET channel complex.

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Acknowledgements

This work was supported by NIH grants R01 HL143297. A.P. is an investigator of the Howard Hughes Medical Institute. We thank J. Grandl, S. Murthy, S. Jojoa-Cruz and A. Gharpure for critical reading of the manuscript.

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J.M.K, A.B.W. and A.P. conceptualized the content of this work. J.M.K. reviewed the literature and drafted the manuscript and figures. J.M.K., A.B.W. and A.P. discussed, wrote and edited the Review.

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Kefauver, J.M., Ward, A.B. & Patapoutian, A. Discoveries in structure and physiology of mechanically activated ion channels. Nature 587, 567–576 (2020). https://doi.org/10.1038/s41586-020-2933-1

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