FAK promotes organization of fibronectin matrix and fibrillar adhesions
Author:
Ilić Duško1, Kovačič Branka2, Johkura Kohei3, Schlaepfer David D.4, Tomašević Nenad5, Han Qin1, Kim Jae-Beom1, Howerton Kyle1, Baumbusch Clark1, Ogiwara Naoko3, Streblow Daniel N.6, Nelson Jay A.6, Dazin Paul7, Shino Yuji8, Sasaki Katsunori39, Damsky Caroline H.110
Affiliation:
1. Department of Stomatology 2. Medicine, 3. Department of Anatomy and Organ Technology, 4. Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA 5. Biochemistry Department, Cytokinetics Inc., South San Francisco, California 94080, USA 6. Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland, Oregon 97201, USA 7. Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143, USA 8. Department of Microbiology, School of Medicine Chiba University, Chiba 260, Japan 9. Institute of Organ Transplants, Reconstructive Medicine and Tissue Engineering, Shinshu University School of Medicine, Matsumoto 390-8621, Japan 10. Anatomy, and the
Abstract
Targeted disruption of the focal adhesion kinase (FAK) gene in mice is lethal at embryonic day 8.5 (E8.5). Vascular defects in FAK-/- mice result from the inability of FAK-deficient endothelial cells to organize themselves into vascular network. We found that, although fibronectin (FN) levels were similar, its organization was less fibrillar in both FAK-/- endothelial cells and mesoderm of E8.5 FAK-/- embryos, as well as in mouse embryonic fibroblasts isolated from mutant embryos. FAK catalytic activity, proline-rich domains, and location in focal contacts were all required for proper allocation and patterning of FN matrix. Cells lacking FAK in focal adhesions fail to translocate supramolecular complexes of integrin-bound FN and focal adhesion proteins along actin filaments to form mature fibrillar adhesions. Taken together, our data suggest that proper FN allocation and organization are dependent on FAK-mediated remodeling of focal adhesions.
Publisher
The Company of Biologists
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