Myosin-X provides a motor-based link between integrins and the cytoskeleton

Nat Cell Biol. 2004 Jun;6(6):523-31. doi: 10.1038/ncb1136. Epub 2004 May 23.

Abstract

Unconventional myosins are actin-based motors with a growing number of attributed functions. Interestingly, it has been proposed that integrins are transported by unidentified myosins to facilitate cellular remodelling. Here we present an interaction between the unconventional myosin-X (Myo10) FERM (band 4.1/ezrin/radixin/moesin) domain and an NPXY motif within beta-integrin cytoplasmic domains. Importantly, knock-down of Myo10 by short interfering RNA impaired integrin function in cell adhesion, whereas overexpression of Myo10 stimulated the formation and elongation of filopodia in an integrin-dependent manner and relocalized integrins together with Myo10 to the tips of filopodia. This integrin relocalization and filopodia elongation did not occur with Myo10 mutants deficient in integrin binding or with a beta(1)-integrin point mutant deficient in Myo10 binding. Taken together, these results indicate that Myo10-mediated relocalization of integrins might serve to form adhesive structures and thereby promote filopodial extension.

Publication types

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

MeSH terms

  • Animals
  • COS Cells
  • Cell Adhesion / genetics
  • Cell Adhesion / physiology*
  • Cell Membrane / genetics
  • Cell Membrane / metabolism
  • Cell Movement / genetics
  • Cell Movement / physiology*
  • Cytoskeleton / metabolism*
  • Cytoskeleton / ultrastructure
  • HeLa Cells
  • Humans
  • Integrin beta1 / metabolism
  • Integrins / genetics
  • Integrins / metabolism*
  • Mice
  • Mutation / genetics
  • Myosins / antagonists & inhibitors
  • Myosins / genetics
  • Myosins / physiology*
  • NIH 3T3 Cells
  • Protein Binding / genetics
  • Protein Structure, Tertiary / physiology
  • Protein Transport / genetics
  • Pseudopodia / metabolism*
  • Pseudopodia / ultrastructure
  • RNA Interference

Substances

  • Integrin beta1
  • Integrins
  • MYO10 protein, human
  • Myo10 protein, mouse
  • Myosins