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Molecular and Cellular Biology, February 2002, p. 901-915, Vol. 22, No. 3
0270-7306/01/$04.00+0     DOI: 10.1128/MCB.22.3.901-915.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The Adaptor Protein Paxillin Is Essential for Normal Development in the Mouse and Is a Critical Transducer of Fibronectin Signaling

Margit Hagel,1 Elizabeth L. George,2 Ann Kim,1 Rulla Tamimi,1 Sarah L. Opitz,2 Christopher E. Turner,3 Akira Imamoto,4 and Sheila M. Thomas1*

Cancer Biology Program, Beth Israel Deaconess Medical Center/Harvard Medical School,1 Vascular Research Division, Department of Pathology, Brigham and Women’s Hospital/Harvard Medical School, Boston, Massachusetts,2 Department of Anatomy and Cell Biology, SUNY—Syracuse, Syracuse, New York,3 Department of Molecular Oncology/Ben May Institute, University of Chicago, Chicago, Illinois4

Received 26 April 2001/ Returned for modification 13 June 2001/ Accepted 21 September 2001

The integrin family of cell adhesion receptors are important for a diverse set of biological responses during development. Although many integrins have been shown to engage a similar set of cytoplasmic effector proteins in vitro, the importance of these proteins in the biological events mediated by different integrin receptors and ligands is uncertain. We have examined the role of one of the best-characterized integrin effectors, the focal adhesion protein paxillin, by disruption of the paxillin gene in mice. Paxillin was found to be critically involved in regulating the development of mesodermally derived structures such as heart and somites. The phenotype of the paxillin-/- mice closely resembles that of fibronectin-/- mice, suggesting that paxillin is a critical transducer of signals from fibronectin receptors during early development. Paxillin was also found to play a critical role in fibronectin receptor biology ex vivo since cultured paxillin-null fibroblasts display abnormal focal adhesions, reduced cell migration, inefficient localization of focal adhesion kinase (FAK), and reduced fibronectin-induced phosphorylation of FAK, Cas, and mitogen-activated protein kinase. In addition, we found that paxillin-null fibroblasts show some defects in the cortical cytoskeleton and cell spreading on fibronectin, raising the possibility that paxillin could play a role in structures distinct from focal adhesions. Thus, paxillin and fibronectin regulate some common embryonic developmental events, possibly due to paxillin modulation of fibronectin-regulated focal adhesion dynamics and organization of the membrane cytoskeletal structures that regulate cell migration and spreading.

* Corresponding author. Mailing address: 330 Brookline Ave., HIM 1047, Boston, MA 02215. Phone: (617) 667-4174. Fax: (617) 667-0610. E-mail: sthomas{at}bidmc.harvard.edu.

Molecular and Cellular Biology, February 2002, p. 901-915, Vol. 22, No. 3
0022-538X/01/$04.00+0     DOI: 10.1128/MCB.22.3.901-915.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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