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J. Cell Biol. 156 (2): 349-360

Copyright © 2002 by the Rockefeller University Press.

Article

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

Olga Krylyshkina1, Irina Kaverina1, Wolfgang Kranewitter1, Walter Steffen2, Maria C. Alonso3, Robert A. Cross3, and J. Victor Small1

1 Institute of Molecular Biology, Austrian Academy of Sciences, Billrothsthstrasse 11, Salzburg 5020, Austria
2 MRC Muscle and Cell Motility Unit, King's College London, Guy's Campus, London, SE1 1UL, UK
3 Marie Curie Research Institute, The Chart, Oxted, Surrey RH8 OTL, UK

Address correspondence to J.V. Small, Dept. of Cell Biology, Institute of Molecular Biology, Austrian Academy of Sciences, Billrothstrasse 11, Salzburg 5020, Austria. Tel.: 43-662-63961-11. Fax: 43-662-63961-40. E-mail: jvsmall{at}imb.oeaw.ac.at

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.

Key Words: microtubules; kinesin; actin cytoskeleton; adhesion; signalling

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