Mechanosensation provides two of the 5 fundamental senses integral to human sensation-touch and hearing. Surprisingly, the seemingly simple sense of """"""""touch"""""""" lacks a satisfactory molecular description in eukaryotes. The question remains: How do molecules in a cell sense and transduce mechanical force in tissue? In mammals ion channels are believed to play a role in mechanosensation;however, studies of mechanosensitive channels have failed to identify a clear structural domain or feature responsible for sensing mechanical force. Absent a clear mechanism for mechanosensation in humans, testable hypotheses are needed to arrive at a correct model. This proposal presents an argument that lipid interactions with ion channels are important to mechano sensation. Forming a molecular description of force transduction will, one, complete our understanding of sensory perception and, two, reveal targets for therapeutic intervention in pain and hearing loss.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
NIH Director’s New Innovator Awards (DP2)
Project #
1DP2NS087943-01
Application #
8572786
Study Section
Special Emphasis Panel (ZRG1-MOSS-C (56))
Program Officer
Silberberg, Shai D
Project Start
2013-09-30
Project End
2018-07-31
Budget Start
2013-09-30
Budget End
2018-07-31
Support Year
1
Fiscal Year
2013
Total Cost
$2,835,000
Indirect Cost
$1,335,000
Name
Scripps Florida
Department
Type
DUNS #
148230662
City
Jupiter
State
FL
Country
United States
Zip Code
33458
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Petersen, E Nicholas; Chung, Hae-Won; Nayebosadri, Arman et al. (2016) Kinetic disruption of lipid rafts is a mechanosensor for phospholipase D. Nat Commun 7:13873
Hansen, Scott B (2015) Lipid agonism: The PIP2 paradigm of ligand-gated ion channels. Biochim Biophys Acta 1851:620-8