Integrin ?11 cytoplasmic tail is required for FAK activation to initiate 3D cell invasion and ERK-mediated cell proliferation.

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

SUBMITTER: Erusappan P 

PROVIDER: S-EPMC6814791 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature