Voltage gating of mechanosensitive PIEZO channels
Mirko Moroni, M. Rocio Servin-Vences, Raluca Fleischer, Oscar Sánchez-Carranza & Gary R. Lewin
Nature Communications volume 9, Article number: 1096 (2018)
doi:10.1038/s41467-018-03502-7
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Ion channels in the nervous system Ion transport Mechanisms of disease Peripheral vascular disease Permeation and transport
Received: 17 August 2017 Accepted: 19 February 2018
Published online: 15 March 2018
Source/Fonte: Ardem Patapoutian
Abstract
Mechanosensitive PIEZO ion channels are evolutionarily conserved proteins whose presence is critical for normal physiology in multicellular organisms. Here we show that, in addition to mechanical stimuli, PIEZO channels are also powerfully modulated by voltage and can even switch to a purely voltage-gated mode. Mutations that cause human diseases, such as xerocytosis, profoundly shift voltage sensitivity of PIEZO1 channels toward the resting membrane potential and strongly promote voltage gating. Voltage modulation may be explained by the presence of an inactivation gate in the pore, the opening of which is promoted by outward permeation. Older invertebrate (fly) and vertebrate (fish) PIEZO proteins are also voltage sensitive, but voltage gating is a much more prominent feature of these older channels. We propose that the voltage sensitivity of PIEZO channels is a deep property co-opted to add a regulatory mechanism for PIEZO activation in widely different cellular contexts.
Acknowledgements
We thank Prof. Thomas Baukrowitz for initial comments on the manuscript. Liana Kozitzki for technical assistance. This work was supported by an Alexander von Humboldt fellowship to M.M. and a Deutsche Forschungsgemeinschaft Collaborative Research Grant to G.R.L. (Project A9 SFB 958).
Author information
Affiliations
Department of Neuroscience, Max-Delbrück Center for Molecular Medicine, Robert-Rössle Straße 10, D-13092, Berlin, Germany
Mirko Moroni, M. Rocio Servin-Vences, Raluca Fleischer, Oscar Sánchez-Carranza & Gary R. Lewin
Excellence Cluster Neurocure, Charité Universitätsmedizin, 10117, Berlin, Germany
Gary R. Lewin
Contributions
Conceptualization: M.M. and G.R.L. Methodology: M.M. Investigation: M.M., M.R.S.-V., R.F., O.S.-C. Writing: M.M. and G.R.L. Visualization: M.M., M.R.S.-V and R.F. Supervision: M.M. and G.R.L. Project administration: M.M. Funding acquisition: G.R.L.
Competing interests
The authors declare no competing interests.
Corresponding authors
Correspondence to Mirko Moroni or Gary R. Lewin.
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