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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS083174-01A1
Application #
8369634
Study Section
Biophysics of Neural Systems Study Section (BPNS)
Program Officer
Silberberg, Shai D
Project Start
2012-09-30
Project End
2017-06-30
Budget Start
2012-09-30
Budget End
2013-06-30
Support Year
1
Fiscal Year
2012
Total Cost
$414,531
Indirect Cost
$195,781
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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