Function of the Tetraspanin CD151–α6β1 Integrin Complex during Cellular Morphogenesis

Upon plating on basement membrane Matrigel, NIH3T3 cells formed an anastomosing network of cord-like structures, inhibitable by anti-α6β1 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 α6β1 were physically associated within NIH3T3 cells. On removal of the short 8-amino acid C-terminal CD151 tail (by deletion or exchange), exogenous CD151 exerted a dominant negative effect, as it almost completely suppressed α6β1-dependent cell network formation and NIH3T3 cell spreading on laminin-1 (an α6β1 ligand). Importantly, mutant CD151 retained α6β1 association and did not alter α6β1-mediated cell adhesion to Matrigel. In conclusion, the CD151–α6β1 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 α6β1-integrin that follow ligand engagement. Also, antibodies to α6β1 and CD151 inhibited formation of endothelial cell cord-like networks, thus pointing to possible relevance of CD151–α6β1 complexes during angiogenesis