Stereocilia-staircase spacing is influenced by myosin III motors and their cargos espin-1 and espin-like

Nat Commun. 2016 Mar 1;7:10833. doi: 10.1038/ncomms10833.

Abstract

Hair cells tightly control the dimensions of their stereocilia, which are actin-rich protrusions with graded heights that mediate mechanotransduction in the inner ear. Two members of the myosin-III family, MYO3A and MYO3B, are thought to regulate stereocilia length by transporting cargos that control actin polymerization at stereocilia tips. We show that eliminating espin-1 (ESPN-1), an isoform of ESPN and a myosin-III cargo, dramatically alters the slope of the stereocilia staircase in a subset of hair cells. Furthermore, we show that espin-like (ESPNL), primarily present in developing stereocilia, is also a myosin-III cargo and is essential for normal hearing. ESPN-1 and ESPNL each bind MYO3A and MYO3B, but differentially influence how the two motors function. Consequently, functional properties of different motor-cargo combinations differentially affect molecular transport and the length of actin protrusions. This mechanism is used by hair cells to establish the required range of stereocilia lengths within a single cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Ear, Inner / metabolism
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Myosin Heavy Chains / genetics
  • Myosin Heavy Chains / metabolism*
  • Myosin Type III / genetics
  • Myosin Type III / metabolism*
  • Rats
  • Stereocilia / physiology*
  • Tissue Culture Techniques

Substances

  • MYO3A protein, mouse
  • MYO3B protein, mouse
  • Microfilament Proteins
  • espin protein, mouse
  • Myosin Type III
  • Myosin Heavy Chains