Talin1 is critical for force-dependent reinforcement of initial integrin–cytoskeleton bonds but not tyrosine kinase activation

• DOI: 10.1083/jcb.200302001
• Publication Date: 2003-10-28T07:13:57Z
• Authors: Grégory Giannone; Guoying Jiang; Deborah H. Sutton; David R. Critchley; Michael P. Sheetz
• Keywords: 0301 basic medicine; Focal Adhesions; Integrins; Filamins; Microfilament Proteins; Phosphoproteins; Models, Biological; Article; Cell Line; Fibronectins; Enzyme Activation; Cytoskeletal Proteins; 03 medical and health sciences; Contractile Proteins; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Cell Adhesion; Humans; Paxillin; Cell Adhesion Molecules; Melanoma; Cytoskeleton; Cell Line, Transformed

Cells rapidly transduce forces exerted on extracellular matrix contacts into tyrosine kinase activation and recruitment of cytoskeletal proteins to reinforce integrin–cytoskeleton connections and initiate adhesion site formation. The relationship between these two processes has not been defined, particularly at the submicrometer level. Using talin1-deficient cells, it appears that talin1 is critical for building early mechanical linkages. Deletion of talin1 blocked laser tweezers, force-dependent reinforcement of submicrometer fibronectin-coated beads and early formation of adhesion sites in response to force, even though Src family kinases, focal adhesion kinase, and spreading were activated normally. Recruitment of vinculin and paxillin to sites of force application also required talin1. FilaminA had a secondary role in strengthening fibronectin–integrin–cytoskeleton connections and no role in stretch-dependent adhesion site assembly. Thus, force-dependent activation of tyrosine kinases is independent of early force-dependent structural changes that require talin1 as part of a critical scaffold.