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Microtubule-induced focal adhesion disassembly is mediated by dynamin and focal adhesion kinase

Nature Cell Biology volume 7, pages 581–590 (2005)Cite this article

Abstract

Imaging studies implicate microtubule targeting of focal adhesions in focal adhesion disassembly, although the molecular mechanism is unknown. Here, we develop a model system of focal adhesion disassembly based on the finding that microtubule regrowth after nocodazole washout induces disassembly of focal adhesions, and that this disassembly occurs independently of Rho and Rac, but depends on focal adhesion kinase (FAK) and dynamin. During disassembly, dynamin interacts with FAK and colocalizes with focal adhesions. Inhibition of dynamin prevents migration of cells with a focal adhesion phenotype. Our results show that focal adhesion disassembly involves microtubules, dynamin and FAK, and is not simply the reversal of focal adhesion formation.

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Figure 1: Microtubule regrowth induces focal adhesion disassembly.
Figure 2: Dynamics of GFP–β1-integrin during microtubule regrowth after nocodazole washout.
Figure 3: Microtubule-induced disassembly of focal adhesions is independent of Rho and Rac.
Figure 4: Microtubule-induced disassembly of focal adhesions is dependent on dynamin.
Figure 5: Dynamin is colocalized near focal adhesions and interacts with FAK during microtubule-induced focal adhesion disassembly.
Figure 6: FAK enhances dynamin localization to focal adhesions and rescues defective microtubule-induced disassembly in the FAK−/− fibroblasts.
Figure 7: Expression of dominant-negative dynamin inhibits directed cell migration into a wound.

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Acknowledgements

We thank the members of the laboratory, and E. Marcantonio and R. Vallee for critically reading the manuscript. We are indebted to R. Vallee for dynamin constructs and antibodies. Supported by NIH grant GM68595 (G.G.G.).

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, Columbia University, 630 West 168th Street, BB 1217, New York, 10032, NY, USA

    Ellen J. Ezratty & Gregg G. Gundersen

  2. Department of Pathology, Columbia University, 630 West 168th Street, BB 1217, New York, 10032, NY, USA

    Michael A. Partridge & Gregg G. Gundersen

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Correspondence to Gregg G. Gundersen.

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Ezratty, E., Partridge, M. & Gundersen, G. Microtubule-induced focal adhesion disassembly is mediated by dynamin and focal adhesion kinase. Nat Cell Biol 7, 581–590 (2005). https://doi.org/10.1038/ncb1262

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