Modulation of substrate adhesion dynamics via microtubule targeting requires kinesin-1

J Cell Biol. 2002 Jan 21;156(2):349-59. doi: 10.1083/jcb.200105051. Epub 2002 Jan 21.

Abstract

Recent studies have shown that the targeting of substrate adhesions by microtubules promotes adhesion site disassembly (Kaverina, I., O. Krylyshkina, and J.V. Small. 1999. J. Cell Biol. 146:1033-1043). It was accordingly suggested that microtubules serve to convey a signal to adhesion sites to modulate their turnover. Because microtubule motors would be the most likely candidates for effecting signal transmission, we have investigated the consequence of blocking microtubule motor activity on adhesion site dynamics. Using a function-blocking antibody as well as dynamitin overexpression, we found that a block in dynein-cargo interaction induced no change in adhesion site dynamics in Xenopus fibroblasts. In comparison, a block of kinesin-1 activity, either via microinjection of the SUK-4 antibody or of a kinesin-1 heavy chain construct mutated in the motor domain, induced a dramatic increase in the size and reduction in number of substrate adhesions, mimicking the effect observed after microtubule disruption by nocodazole. Blockage of kinesin activity had no influence on either the ability of microtubules to target substrate adhesions or on microtubule polymerisation dynamics. We conclude that conventional kinesin is not required for the guidance of microtubules into substrate adhesions, but is required for the focal delivery of a component(s) that retards their growth or promotes their disassembly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Movement
  • Dyneins / metabolism
  • Fibroblasts
  • Focal Adhesions*
  • Humans
  • Kinesins / antagonists & inhibitors
  • Kinesins / genetics
  • Kinesins / metabolism*
  • Membrane Glycoproteins / metabolism*
  • Membrane Potentials
  • Mice
  • Microscopy, Video
  • Microtubules / drug effects
  • Microtubules / metabolism*
  • Molecular Motor Proteins / metabolism
  • Mutagenesis
  • Nocodazole / pharmacology
  • Polymerase Chain Reaction
  • Protein Binding
  • Rats
  • Xenopus / metabolism*

Substances

  • Membrane Glycoproteins
  • Molecular Motor Proteins
  • substrate adhesion molecules
  • Dyneins
  • Kinesins
  • Nocodazole