A new compartment at stereocilia tips defined by spatial and temporal patterns of myosin IIIa expression

J Neurosci. 2006 Oct 4;26(40):10243-52. doi: 10.1523/JNEUROSCI.2812-06.2006.

Abstract

Class III myosins are motor proteins that contain an N-terminal kinase domain and a C-terminal actin-binding domain. We show that myosin IIIa, which has been implicated in nonsyndromic progressive hearing loss, is localized at stereocilia tips. Myosin IIIa progressively accumulates during stereocilia maturation in a thimble-like pattern around the stereocilia tip, distinct from the cap-like localization of myosin XVa and the shaft localization of myosin Ic. Overexpression of deletion mutants for functional domains of green fluorescent protein (GFP)-myosin IIIa shows that the motor domain, but not the actin-binding tail domain, is required for stereocilia tip localization. Deletion of the kinase domain produces stereocilia elongation and bulging of the stereocilia tips. The thimble-like localization and the influence myosin IIIa has on stereocilia shape reveal a previously unrecognized molecular compartment at the distal end of stereocilia, the site of actin polymerization as well as operation of the mechanoelectrical transduction apparatus.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anura
  • Bass
  • COS Cells
  • Cells, Cultured
  • Chickens
  • Chlorocebus aethiops
  • Cilia / genetics
  • Cilia / metabolism
  • Ear, Inner / metabolism*
  • Gene Expression Regulation, Developmental / physiology*
  • Guinea Pigs
  • Humans
  • Mice
  • Myosin Heavy Chains / biosynthesis*
  • Myosin Heavy Chains / genetics
  • Myosin Type III / biosynthesis*
  • Myosin Type III / genetics
  • Rats
  • Time Factors

Substances

  • MYO3A protein, human
  • Myosin Type III
  • Myosin Heavy Chains