Abstract

The global objective of this research application is to provide new insights into the mechanism by which the membrane protein prestin confers electromotile properties to outer hair cells (OHCs). It has been proposed that OHC electromotility functions as the cochlear amplifier in mammalian hearing, and that damage to OHCs results in distinct and dramatic hearing loss. This study will examine the behavior of prestin in the plasma membrane, specifically focusing on the lateral mobility or diffusion of the protein in several cellular systems under various environmental conditions. Mobility studies will be conducted using the powerful and established technique of fluorescence recovery after photobleaching (FRAP). Individual experiments will focus on how lateral diffusion is affected by membrane cholesterol concentration, small anion concentrations, salicylate and chlorpromazine, as well as membrane tension experiments. We hypothesize these perturbations produce alterations in plasma membrane properties, which influence the behavior of prestin. The results of these studies will provide valuable information about how the plasma membrane environment 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 #
5F31DC008058-03
Application #
7271353
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
2007
Total Cost
$8,314
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