Pinon et al. clarify the sequence of events during integrin-mediated cell spreading.
When a moving cell finds itself on an unfamiliar substrate, integrin receptors in the plasma membrane first get a grip on the surface. Then the integrins begin to signal, spurring the cell to spread out and make itself at home. Analyzing the connection between the two functions has been difficult because integrin mutations that disrupt one process usually thwart the other. One important protein in these processes is talin, which latches onto integrins and helps to lock them in an active posture. Other proteins such as paxillin and focal adhesion kinase (FAK) arrive at cell surface junctions to trigger spreading and detect forces acting on the cell. Researchers have been unsure about whether these proteins are present at the same time and how they interact, however.
Pinon et al. were able to isolate the two processes—holding on and spreading out—using engineered integrins that bind talin tightly. Cells carrying these integrins could fasten to a surface and settle down. But when the researchers analyzed mutations in the engineered integrins, they identified cells that were only capable of attachment, not spreading. Mutations that thwarted cell spreading also prevented integrins from binding to paxillin. Furthermore, cells didn’t stretch out if they harbored altered integrins that couldn’t bind to kindlin, a protein that helps activate the receptors.
The results suggest that talin doesn’t have to disconnect from integrins before paxillin and FAK can bind. Instead, talin and kindlin first grab onto integrins, forming a platform that allows paxillin and FAK to join them. The findings might provide new insights into how the control of cell attachment and spreading goes wrong in cancer.
Text by Mitch Leslie