For sense of touch/pain and hearing, cation channels that are directly activated in response to mechanical forces have been characterized. In addition, many other cell types including vascular smooth muscle cells express such mechanically-activated (MA) cationic currents, and mechanotransduction is implicated in various biological processes and diseases. Remarkably, however, the identity of these ion channels in vertebrates has remained unknown. We recently identified MA cation channel components in vertebrates named Piezo1 and Piezo2. Expressing Piezos in a variety of mammalian cell lines induce large MA cationic currents. Piezos are expressed in a variety of tissues implicated in mechanotransduction. Piezo1 and Piezo2 contain over 24 putative transmembrane domains but do not resemble known ion channels or other protein classes. Many important open questions remain about the structure of these proteins. Here, we hypothesize that Piezo1 oligomerizes to form pore-containing subunits of mechanically-activated ion channels.

Public Health Relevance

Mechanotransduction impacts a variety of biological systems and diseases, and is linked to hearing and deafness, inflammatory pain states, cardiovascular disease, osteoporosis. Indeed, many cells use mechanosensitivity to coordinate cell and tissue growth, and failure of these mechanisms may contribute to cancer and other pathologies. Therefore, a molecular understanding of mechanical sensation is important and relevant to a variety of medical indications.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Biophysics of Neural Systems Study Section (BPNS)
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Silberberg, Shai D
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Scripps Research Institute
La Jolla
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Saotome, Kei; Murthy, Swetha E; Kefauver, Jennifer M et al. (2018) Structure of the mechanically activated ion channel Piezo1. Nature 554:481-486
Kefauver, Jennifer M; Saotome, Kei; Dubin, Adrienne E et al. (2018) Structure of the human volume regulated anion channel. Elife 7:
Dubin, Adrienne E; Murthy, Swetha; Lewis, Amanda H et al. (2017) Endogenous Piezo1 Can Confound Mechanically Activated Channel Identification and Characterization. Neuron 94:266-270.e3
Syeda, Ruhma; Florendo, Maria N; Cox, Charles D et al. (2016) Piezo1 Channels Are Inherently Mechanosensitive. Cell Rep 17:1739-1746
Syeda, Ruhma; Qiu, Zhaozhu; Dubin, Adrienne E et al. (2016) LRRC8 Proteins Form Volume-Regulated Anion Channels that Sense Ionic Strength. Cell 164:499-511
Lukacs, Viktor; Mathur, Jayanti; Mao, Rong et al. (2015) Impaired PIEZO1 function in patients with a novel autosomal recessive congenital lymphatic dysplasia. Nat Commun 6:8329
Syeda, Ruhma; Xu, Jie; Dubin, Adrienne E et al. (2015) Chemical activation of the mechanotransduction channel Piezo1. Elife 4:
Coste, Bertrand; Murthy, Swetha E; Mathur, Jayanti et al. (2015) Piezo1 ion channel pore properties are dictated by C-terminal region. Nat Commun 6:7223
Cahalan, Stuart M; Lukacs, Viktor; Ranade, Sanjeev S et al. (2015) Piezo1 links mechanical forces to red blood cell volume. Elife 4:
Albuisson, Juliette; Murthy, Swetha E; Bandell, Michael et al. (2013) Dehydrated hereditary stomatocytosis linked to gain-of-function mutations in mechanically activated PIEZO1 ion channels. Nat Commun 4:1884