Myosin-XVa is required for tip localization of whirlin and differential elongation of hair-cell stereocilia

Inna A. Belyantseva, Erich T. Boger, Sadaf Naz, Gregory I. Frolenkov, James R. Sellers, Zubair M. Ahmed, Andrew J. Griffith, Thomas B. Friedman

Research output: Contribution to journalArticlepeer-review

279 Scopus citations

Abstract

Stereocilia are microvilli-derived mechanosensory organelles that are arranged in rows of graded heights on the apical surface of inner-ear hair cells. 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 mice4-6. 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.

Original languageEnglish
Pages (from-to)148-156
Number of pages9
JournalNature Cell Biology
Volume7
Issue number2
DOIs
StatePublished - Feb 2005

Bibliographical note

Funding Information:
We thank R. Chadwick, D. Drayna, R. Morell and D. Wu for their critical reading of the manuscript. We also thank R. Cheney (from the University of North Carolina at Chapel Hill) for providing the bovine Myo10 cDNA expression construct. This study was supported by intramural research funds from the National Institute on Deafness and Other Communication Disorders and the National Institutes of Health (to A.J.G. and T.B.F.).

ASJC Scopus subject areas

  • Cell Biology

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