Abstract

The global objective of this research proposal is to provide new insights into the mechanism by which themembrane protein prestin confers electromotile properties to outer hair cells (OHCs). It has been proposedthat OHC electromotility functions as the cochlear amplifier in mammalian hearing, and damage to OHCsresults in distinct and dramatic hearing loss. This study will examine the behavior of prestin in the plasmamembrane, specifically focusing on the lateral mobility or diffusion of the protein in several cellular systemsunder various environmental conditions. Mobility studies will be conducted using the powerful andestablished technique of fluorescence recovery after photobleaching (FRAP). Individual experiments willfocus on how lateral diffusion is affected by membrane cholesterol concentration, small anionconcentrations, salicylate and chlorpromazine, as well as membrane tension experiments. We hypothesizethese perturbations produce alterations in plasma membrane properties, which influence the behavior ofprestin. The results of these studies will provide valuable information about how the plasma membraneenvironment affects and interacts with prestin and will shed light on the action of ototoxic drugs.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
3F31DC008058-03S1
Application #
7534723
Study Section
Communication Disorders Review Committee (CDRC)
Program Officer
Cyr, Janet
Project Start
2005-09-01
Project End
2008-05-15
Budget Start
2007-09-01
Budget End
2008-05-15
Support Year
3
Fiscal Year
2008
Total Cost
$10,755
Indirect Cost

  Institution

Name
Rice University
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
050299031
City
Houston
State
TX
Country
United States
Zip Code
77005

  Publications

Kamar, R I; Organ-Darling, L E; Raphael, R M (2012) Membrane cholesterol strongly influences confined diffusion of prestin. Biophys J 103:1627-36
Rajagopalan, Lavanya; Organ-Darling, Louise E; Liu, Haiying et al. (2010) Glycosylation regulates prestin cellular activity. J Assoc Res Otolaryngol 11:39-51
Organ, Louise E; Raphael, Robert M (2009) Lipid lateral mobility in cochlear outer hair cells: regional differences and regulation by cholesterol. J Assoc Res Otolaryngol 10:383-96
Organ, Louise E; Raphael, Robert M (2007) Application of fluorescence recovery after photobleaching to study prestin lateral mobility in the human embryonic kidney cell. J Biomed Opt 12:021003
Greeson, Jennifer N; Organ, Louise E; Pereira, Fred A et al. (2006) Assessment of prestin self-association using fluorescence resonance energy transfer. Brain Res 1091:140-50