Recreation of the terminal events in physiological integrin activation

Feng Ye, Guiqing Hu, Dianne Taylor, Boris Ratnikov, Andrey A. Bobkov, Mark A. McLean, Stephen G. Sligar, Kenneth A. Taylor, Mark H. Ginsberg

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)157-173
Number of pages17
JournalJournal of Cell Biology
Issue number1
StatePublished - Dec 11 2010

ASJC Scopus subject areas

  • Cell Biology


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