Abstract:
:Dynamic regulation of adhesion complexes is required for cell migration and has therefore emerged as a key issue in the study of cell motility. 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 kinases. 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.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Franco SJ,Rodgers MA,Perrin BJ,Han J,Bennin DA,Critchley DR,Huttenlocher Adoi
10.1038/ncb1175keywords:
subject
Has Abstractpub_date
2004-10-01 00:00:00pages
977-83issue
10eissn
1465-7392issn
1476-4679pii
ncb1175journal_volume
6pub_type
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