Letter abstract
Nature Cell Biology 7, 148 - 156 (2005)
Published online: 16 January 2005 | doi:10.1038/ncb1219
Myosin-XVa is required for tip localization of whirlin and differential elongation of hair-cell stereocilia
Inna A. Belyantseva1,6, Erich T. Boger1,2,6, Sadaf Naz1, Gregory I. Frolenkov3, James R. Sellers4, Zubair M. Ahmed1, Andrew J. Griffith3,5 & Thomas B. Friedman1
Stereocilia are microvilli-derived mechanosensory organelles that are arranged in rows of graded heights on the apical surface of inner-ear hair cells1. The 'staircase'-like architecture of stereocilia bundles is necessary to detect sound and head movement, and is achieved through differential elongation of the actin core of each stereocilium to a predetermined length2, 3. Abnormally short stereocilia bundles that have a diminished staircase are characteristic of the shaker 2 (Myo15ash2) and whirler (Whrnwi) strains of deaf mice4, 5, 6. We show that myosin-XVa is a motor protein that, in vivo, interacts with the third PDZ domain of whirlin through its carboxy-terminal PDZ-ligand. Myosin-XVa then delivers whirlin to the tips of stereocilia. Moreover, if green fluorescent protein (GFP)-Myo15a is transfected into hair cells of Myo15ash2 mice, the wild-type pattern of hair bundles is restored by recruitment of endogenous whirlin to the tips of stereocilia. The interaction of myosin-XVa and whirlin is therefore a key event in hair-bundle morphogenesis.
- Section on Human Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA.
- Department of Biology, University of Maryland, College Park, MD 20742, USA.
- Section on Gene Structure and Function, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA.
- Laboratory of Molecular Physiology, National Heart, Lung, and Blood Institute, Bethesda, MD 20890, USA.
- Hearing Section, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA.
- These authors contibuted equally to this work.
Correspondence to: Thomas B. Friedman1 e-mail: friedman@nidcd.nih.gov
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