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

Nat Cell Biol. 2005 Feb;7(2):148-56. doi: 10.1038/ncb1219. Epub 2005 Jan 16.


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 length. Abnormally short stereocilia bundles that have a diminished staircase are characteristic of the shaker 2 (Myo15a(sh2)) and whirler (Whrn(wi)) strains of deaf mice. 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 Myo15a(sh2) 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism
  • Animals
  • COS Cells
  • Cells, Cultured
  • Chlorocebus aethiops
  • Cilia / ultrastructure*
  • Deafness / genetics*
  • Green Fluorescent Proteins
  • Hair Cells, Auditory, Inner / growth & development*
  • Hair Cells, Auditory, Inner / ultrastructure
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Mutant Strains
  • Models, Biological
  • Molecular Motor Proteins / metabolism
  • Myosins / physiology*


  • Actins
  • Membrane Proteins
  • Molecular Motor Proteins
  • Myo15 protein, mouse
  • Whrn protein, mouse
  • Green Fluorescent Proteins
  • Myosins