Integrin Alpha 11 Cytoplasmic Tail Is Required For Fak Activation To Initiate 3d Cell Invasion And Erk-Mediated Cell Proliferation

Integrin alpha 11 beta 1 is a collagen-binding integrin, which is receiving increasing attention in the context of wound healing and fibrosis. Although alpha 11 beta 1 integrin displays similar collagen specificity to alpha 2 beta 1 integrin, both integrins have distinct in vivo functions. In this context, the contribution of alpha 11 subunit cytoplasmic tail interactions to diverse molecular signals and biological functions is largely unknown. In the current study, we have deleted the alpha 11 cytoplasmic tail and studied the effect of this deletion on alpha 11 integrin function. Compared to wild-type cells, C2C12 cells expressing tail-less alpha 11 attached normally to collagen I, but formed fewer focal contacts. alpha 11-tail-less cells furthermore displayed a reduced capacity to invade and reorganize a 3D collagen matrix and to proliferate. Analysis of cell signaling showed that FAK and ERK phosphorylation was reduced in cells expressing tail-less alpha 11. Inhibition of ERK and FAK activation decreased alpha 11-mediated cell proliferation, whereas alpha 11-mediated cell invasion was FAK-dependent and occurred independently of ERK signaling. In summary, our data demonstrate that the integrin alpha 11 cytoplasmic tail plays a central role in alpha 11 integrin-specific functions, including FAK-dependent ERK activation to promote cell proliferation.