Abstract
Dynamic regulation of adhesion complexes is required for cell migration and has therefore emerged as a key issue in the study of cell motility1. Recent progress has been made in defining some of the molecular mechanisms by which adhesion disassembly is regulated, including the contributions of adhesion adaptor proteins and tyrosine kinases2. However, little is known about the potential contribution of proteolytic mechanisms to the regulation of adhesion complex dynamics. Here, we show that proteolysis of talin by the intracellular calcium-dependent protease calpain is critical for focal adhesion disassembly. We have generated a single point mutation in talin that renders it resistant to proteolysis by calpain. Quantification of adhesion assembly and disassembly rates demonstrates that calpain-mediated talin proteolysis is a rate-limiting step during adhesion turnover. Furthermore, we demonstrate that disassembly of other adhesion components, including paxillin, vinculin and zyxin, is also dependent on the ability of calpain to cleave talin, suggesting a general role for talin proteolysis in regulating adhesion turnover. Together, these findings identify calpain-mediated proteolysis of talin as a mechanism by which adhesion dynamics are regulated.
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References
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Acknowledgements
We would like to thank M. Ginsberg and R. Anderson for reagents and useful discussions, and J. Byrnes for technical assistance. This research was supported by National Institutes of Health grants R01CA85862-01 (A.H.) and T32GM07215-25 (S.J.F. and B.J.P.). Work in the laboratory of D.R.C. was funded by the Wellcome Trust.
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Franco, S., Rodgers, M., Perrin, B. et al. Calpain-mediated proteolysis of talin regulates adhesion dynamics. Nat Cell Biol 6, 977–983 (2004). https://doi.org/10.1038/ncb1175
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DOI: https://doi.org/10.1038/ncb1175
