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- Title
Recreation of the terminal events in physiological integrin activation.
- Authors
Ye, Feng; Hu, Guiqing; Taylor, Dianne; Ratnikov, Boris; Bobkov, Andrey A.; McLean, Mark A.; Sligar, Stephen G.; Taylor, Kenneth A.; Ginsberg, Mark H.
- Abstract
Increased affinity of integrins for the extracellular matrix (activation) regulates cell adhesion and migration, extracellular matrix assembly, and mechanotransduction. Major uncertainties concern the sufficiency of talin for activation, whether conformational change without clustering leads to activation, and whether mechanical force is required for molecular extension. Here, we reconstructed physiological integrin activation in vitro and used cellular, biochemical, biophysical, and ultrastructural analyses to show that talin binding is sufficient to activate integrin αIIbβ3. Furthermore, we synthesized nanodiscs, each bearing a single lipid-embedded integrin, and used them to show that talin activates unclustered integrins leading to molecular extension in the absence of force or other membrane proteins. Thus, we provide the first proof that talin binding is sufficient to activate and extend membrane-embedded integrin αIIbβ3, thereby resolving numerous controversies and enabling molecular analysis of reconstructed integrin signaling.
- Subjects
INTEGRINS; EXTRACELLULAR matrix; CELL adhesion; CELL communication; CELL migration; MOLECULAR structure
- Publication
Journal of Cell Biology, 2010, Vol 188, Issue 1, p157
- ISSN
0021-9525
- Publication type
Article
- DOI
10.1083/jcb.200908045