Directional persistence of migrating cells requires Kif1C-mediated stabilization of trailing adhesions

Dev Cell. 2012 Dec 11;23(6):1153-66. doi: 10.1016/j.devcel.2012.11.005.

Abstract

Directional cell migration requires the establishment and maintenance of long-term differences in structure and function between the front and back of a cell. Here, we show that the microtubule motor Kif1C contributes to persistent cell migration primarily through stabilization of an extended cell rear. Kif1C-mediated transport of α5β1-integrins is required for the proper maturation of trailing focal adhesions and resistance to tail retraction. Tail retraction precedes and induces changes in migration direction. Stabilization of cell tails through inhibition of myosin II activity suppresses the Kif1C depletion phenotype and results in longer-lived tails and higher directional stability of migrating cells. Taken together, these findings indicate that the maintenance of an extended, tense cell tail facilitates directional migration. We propose a rear drag mechanism for directional persistence of migration whereby the counterforce originating from a well-anchored tail serves to maintain directionality of the force-generating leading edge of the cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion / physiology
  • Cell Line
  • Cell Movement / physiology*
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Focal Adhesions / metabolism
  • Humans
  • Integrin alpha5beta1 / metabolism*
  • Kinesin / metabolism*
  • Microtubules / metabolism
  • Myosin Type II / metabolism
  • Protein Transport
  • Retinal Pigment Epithelium / cytology

Substances

  • Integrin alpha5beta1
  • KIF1C protein, human
  • Myosin Type II
  • Kinesin