Mechanotransduction has an important role in physiology. Biological processes including sensing touch and sound waves require as-yet-unidentified cation channels that detect pressure. Mouse Piezo1 (MmPiezo1) and MmPiezo2 (also called Fam38a and Fam38b, respectively) induce mechanically activated cationic currents in cells; however, it is unknown whether Piezo proteins are pore-forming ion channels or modulate ion channels. Here we show that Drosophila melanogaster Piezo (DmPiezo, also called CG8486) also induces mechanically activated currents in cells, but through channels with remarkably distinct pore properties including sensitivity to the pore blocker ruthenium red and single channel conductances. MmPiezo1 assembles as a ∼1.2-million-dalton homo-oligomer, with no evidence of other proteins in this complex. Purified MmPiezo1 reconstituted into asymmetric lipid bilayers and liposomes forms ruthenium-red-sensitive ion channels. These data demonstrate that Piezo proteins are an evolutionarily conserved ion channel family involved in mechanotransduction.
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We thank M. H. Ulbrich for providing Ca2+ channel-, NMDA receptor- and CNG channel–GFP fusion constructs used as controls for photobleaching experiments. This research was supported by grants from the National Institutes of Dental and Craniofacial Research, Neurological Disorders, General Medical Sciences, and by The Genomics Institute of the Novartis Research Foundation. B.X. and J.G. are postdoctoral fellowship recipients from the American Heart Association and the NIH, respectively.
The authors declare no competing financial interests.
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Coste, B., Xiao, B., Santos, J. et al. Piezo proteins are pore-forming subunits of mechanically activated channels. Nature 483, 176–181 (2012). https://doi.org/10.1038/nature10812
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