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A more recent version of this article appeared on January 1, 2002
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Submitted on July 17, 2001
Revised on October 2, 2001
Accepted on October 5, 2001
6 ß1 Integrin
Complex During Cellular Morphogenesis
1 Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, Massachusetts, (present address: Vascular Biology Center, University of Tennessee Health Science Center, Memphis, Tennessee)
2 Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, Massachusetts
* Corresponding author. E-mail address: martin_hemler{at}dfci.harvard.edu.
Upon plating on basement membrane Matrigel, NIH3T3 cells formed an anastomosing network of cord-like structures, inhibitable by anti-6 ß1 integrin antibodies. For NIH3T3 cells transfected with human CD151 protein, the formation of a cord-like network was also inhibitable by anti-CD151 antibodies. Furthermore, CD151 and 6 ß1 were physically associated within NIH3T3 cells. Upon removal of the short 8 aa C-terminal CD151 tail (by deletion or exchange), exogenous CD151 exerted a dominant negative effect, as it almost completely suppressed 6 ß1-dependent cell network formation, and NIH3T3 cell spreading on laminin-1 (an 6 ß1 ligand). Importantly, mutant CD151 retained 6 ß1 association and did not alter (6(1-mediated cell adhesion to Matrigel. In conclusion, the CD151-6 ß1 integrin complex acts as a functional unit that markedly influences cellular morphogenesis, with the CD151 tail being of particular importance in determining the "outside-in" functions of 6 ß1-integrin that follow ligand engagement. Also, antibodies to 6 ß1 and CD151 inhibited formation of endothelial cell cord-like networks, thus pointing to possible relevance of CD151-6 ß1 complexes during angiogenesis.
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