Recreation of the terminal events in physiological integrin activation

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 acti...

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Bibliographic Details
Published in:The Journal of cell biology 2010-01, Vol.188 (1), p.157-173
Main Authors: Ye, Feng, Hu, Guiqing, Taylor, Dianne, Ratnikov, Boris, Bobkov, Andrey A, McLean, Mark A, Sligar, Stephen G, Taylor, Kenneth A, Ginsberg, Mark H
Format: Article
Language:English
Subjects:
Animals
Antibodies
Cell adhesion & migration
Cells
CHO Cells
Cricetinae
Cricetulus
Cryoelectron Microscopy
Density
Humans
Image classification
Integrins
Ligands
Lipids
Liposomes
Membranes
Models, Molecular
Molecular biology
Mutation
Nanostructures - ultrastructure
Phospholipids
Platelet Glycoprotein GPIIb-IIIa Complex - chemistry
Platelet Glycoprotein GPIIb-IIIa Complex - genetics
Platelet Glycoprotein GPIIb-IIIa Complex - physiology
Platelet Glycoprotein GPIIb-IIIa Complex - ultrastructure
Platelets
Protein Binding
Protein Structure, Quaternary
Proteins
Teeth
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Summary: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.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.200908045