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First published online 2 December 2003
doi: 10.1242/jcs.00845
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Research Article |
ko Ili
1,*
i
2
evi
5
1 Department of Stomatology, 2 Medicine, and 10 Anatomy, and the 7 Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143, USA
3 Department of Anatomy and Organ Technology, and 9 Institute of Organ Transplants, Reconstructive Medicine and Tissue Engineering, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
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
8 Department of Microbiology, School of Medicine Chiba University, Chiba 260, Japan
* Author for correspondence (e-mail: ilic{at}itsa.ucsf.edu)
Accepted 27 August 2003
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.
Key words: FAK, Fibronectin matrix allocation, Fibrillar adhesions, Focal adhesion dynamics, Motility
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