Journal of Neuroscience Features WVU Illustration
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| Binding of a recombinant fragment of myosin-1c (Myo1c) (green), a component of the hair-cell transduction complex, to an isolated bullfrog saccular hair cell. Filamentous actin is stained in red to delineate the actin-filled stereocilia that comprise the mechanosensitive hair bundle. Note the intense binding of Myo1c to receptors at the tips of stereocilia, the site of hair-cell transduction, as well as binding within the soma. For more information, see the article by Phillips et al. in the October 18, 2006 issue. |
The Journal of Neuroscience — a major influential adacemic journal in the field — last week featured a cover illustration from a recent article authored by several scientists in West Virginia University's Sensory Neuroscience Research Center. The hair cells illustrated in the article form an accidental holiday theme.
More Information at Journal of Neuroscience website.
The article appeard in the Journal of Neuroscience, October 18, 2006 edition.
Stereociliary Myosin-1c Receptors Are Sensitive to Calcium Chelation and Absent from Cadherin 23 Mutant Mice
Kelli R. Phillips,1,2 Song Tong,1,3 Richard Goodyear,4 Guy P. Richardson,4 and Janet L. Cyr1,2,3
- 1 Sensory Neuroscience Research Center and Departments of
- 2 Biochemistry and Molecular Pharmacology and
- 3 Otolaryngology, West Virginia University School of Medicine, Morgantown, West Virginia 26506-9303, and
- 4 School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, United Kingdom
Correspondence should be addressed to:
Dr. Janet L. Cyr, West Virginia University School of Medicine
Sensory Neuroscience Research Center
P.O. Box 9303
One Medical Center Drive
Morgantown, WV 26506-9303
E-mail: jcyr@hsc.wvu.edu
The identities of some of the constituents of the hair-cell transduction apparatus have been elucidated only recently. The molecular motor myosin-1c (Myo1c) functions in adaptation of the hair-cell response to sustained mechanical stimuli and is therefore an integral part of the transduction complex. Recent data indicate that Myo1c interacts in vitro with two other molecules proposed to be important for transduction: cadherin 23 (Cdh23), a candidate for the stereociliary tip link, and phosphatidylinositol 4,5-bisphosphate (PIP2), which is abundant in the membranes of hair-cell stereocilia. It is not known, however, whether these interactions occur in hair cells. Using an in situ binding assay on saccular hair cells, we demonstrated previously that Myo1c interacts with molecules at stereociliary tips, the site of transduction, through sequences contained within its calmodulin (CaM)-binding neck domain, which can bind up to four CaM molecules. In the current study, we identify the second CaM-binding IQ domain as a region of Myo1c that mediates CaM-sensitive binding to stereociliary tips and to PIP2 immobilized on a solid support. Binding of Myo1c to stereociliary tips of cochlear and vestibular hair cells is disrupted by treatments that break tip links. In addition, Myo1c does not bind to stereocilia from mice whose hair cells lack Cdh23 protein despite the presence of PIP2 in the stereociliary membranes. Collectively, our data suggest that Myo1c and Cdh23 interact at the tips of hair-cell stereocilia and that this interaction is modulated by CaM.
Correspondence should be addressed to:
Dr. Janet L. Cyr, West Virginia University School of Medicine
Sensory Neuroscience Research Center
P.O. Box 9303
One Medical Center Drive
Morgantown, WV 26506-9303
E-mail: jcyr@hsc.wvu.edu
The Sensory Neuroscience Research Center
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