Talin’s tail controls cell cycle
P. Wang, C. Ballestrem, and C.H. Streuli. (2011). The C terminus of talin links integrins to cell cycle progression. J Cell Biol. 195, 499-513. JCB
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Integrins have crucial roles in sensing the ECM environment and delivering signals to control how cells behave. It was known for a long time that integrins are essential for cell cycle, but it was not well understood which components within the integrin adhesion complex are involved. In this study we identified an important role for the adhesion complex protein called talin in this process.
Talin has received considerable attention because it is the molecule that activates integrins to bind ECM proteins, and it does this via its amino-terminal head domain. We have now discovered that the other end of the protein, its carboxy-terminal tail, has a different function. We found that this domain coordinates the recruitment and phosphorylation of key adhesion complex components, including focal adhesion kinase. Our work also showed that integrins, talin, and focal adhesion kinase affect cell cycle by regulating the levels of p21, which is a protein that inhibits cyclin dependent kinases and thereby directly determines progression through the G1/S phases of the cell cycle.
Our new findings mean that talin is a multi-functional signal transducer within the integrin adhesion complex. One part of the molecule, its head, mediates outward conformational changes to activate integrins, while another part, the tail, links both to the cytoskeleton and to intracellular pathways required for cell cycle progression.
The study helps to explain how integrin adhesions work, and it provides new insights into the function of a large scaffold molecule, which has different regions for activating integrins, linking to the cytoskeleton, and delivering intracellular signals. We also found that talin also has a role in cell cycle regulation of a metastatic mammary cancer line, lending credence to the idea that targeting proteins downstream of integrins might represent a therapeutic route of intervention in cancer patients.