Myosin-1c (Myo1c) is essential to the mechanosensitive process of slow adaptation that occurs during transduction in hair cells, the sensory receptor cells of the inner ear. Previous data, using T701, a protein fragment consisting of Myo1c neck and tail domains, has shown that Myo1c interacts with other components of the transduction complex, termed """"""""receptors,"""""""" through its neck domain. This domain is also known to interact with calmodulin (CaM), and excess CaM has been shown to disrupt Myo1c interactions with receptors. Myo1c has also been shown to interact, in a tissue culture cell line, with cadherin 23 (Cdh23), a cell-adhesion protein recently shown to be part of the transduction complex. The goal of this research is to describe Myo1c's interactions with unidentified hair-cell receptors and Cdh23. To further characterize CaM's regulation of Myo1c interactions with receptors, directed mutations to the neck region of Myo1c will be made in the context of T701. In addition, identical mutations will be made in the context of full-length Myo1c and tested in ATPase and motility assays. Finally, the proposed interaction between Myo1c and Cdh23 will be explored within the context of the hair cell.

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 #
1F31DC007558-01
Application #
6935778
Study Section
Communication Disorders Review Committee (CDRC)
Program Officer
Sklare, Dan
Project Start
2005-01-01
Project End
2006-12-31
Budget Start
2005-01-01
Budget End
2005-12-31
Support Year
1
Fiscal Year
2005
Total Cost
$27,684
Indirect Cost
Name
West Virginia University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
191510239
City
Morgantown
State
WV
Country
United States
Zip Code
26506
Phillips, Kelli R; Cyr, Janet L (2007) In situ binding assay to detect Myosin-1c interactions with hair-cell proteins. Methods Mol Biol 392:117-31
Phillips, Kelli R; Tong, Song; Goodyear, Richard et al. (2006) Stereociliary myosin-1c receptors are sensitive to calcium chelation and absent from cadherin 23 mutant mice. J Neurosci 26:10777-88