The Abl-related gene (Arg) requires its F-actin-microtubule cross-linking activity to regulate lamellipodial dynamics during fibroblast adhesion

J Cell Biol. 2004 May 10;165(3):407-19. doi: 10.1083/jcb.200308055.

Abstract

Microtubules (MTs) help establish and maintain cell polarity by promoting actin-dependent membrane protrusion at the leading edge of the cell, but the molecular mechanisms that mediate cross-talk between actin and MTs during this process are unclear. We demonstrate that the Abl-related gene (Arg) nonreceptor tyrosine kinase is required for dynamic lamellipodial protrusions after adhesion to fibronectin. arg-/- fibroblasts exhibit reduced lamellipodial dynamics as compared with wild-type fibroblasts, and this defect can be rescued by reexpression of an Arg-yellow fluorescent protein fusion. We show that Arg can bind MTs with high affinity and cross-link filamentous actin (F-actin) bundles and MTs in vitro. MTs concentrate and insert into Arg-induced F-actin-rich cell protrusions. Arg requires both its F-actin-binding domains and its MT-binding domain to rescue the defects in lamellipodial dynamics of arg-/- fibroblasts. These findings demonstrate that Arg can mediate physical contact between F-actin and MTs at the cell periphery and that this cross-linking activity is required for Arg to regulate lamellipodial dynamics in fibroblasts.

Publication types

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

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actins / metabolism*
  • Actins / ultrastructure
  • Animals
  • Binding Sites / genetics
  • Cell Adhesion / genetics
  • Cell Line, Transformed
  • Cell Movement / genetics
  • Fibroblasts / metabolism*
  • Fibroblasts / ultrastructure
  • Fibronectins / metabolism
  • Gene Expression Regulation / genetics
  • Mice
  • Microtubules / metabolism*
  • Microtubules / ultrastructure
  • Nonlinear Dynamics
  • Protein Binding / genetics
  • Protein Structure, Tertiary / genetics
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Pseudopodia / metabolism*
  • Pseudopodia / ultrastructure

Substances

  • Actins
  • Fibronectins
  • ARG tyrosine kinase
  • Protein-Tyrosine Kinases