Mechanically Activated Integrin Switch Controls α5β1 Function

@article{Friedland2009MechanicallyAI,
  title={Mechanically Activated Integrin Switch Controls $\alpha$5$\beta$1 Function},
  author={Julie C. Friedland and Mark H. Lee and David Boettiger},
  journal={Science},
  year={2009},
  volume={323},
  pages={642 - 644}
}
The cytoskeleton, integrin-mediated adhesion, and substrate stiffness control a common set of cell functions required for development and homeostasis that are often deranged in cancer. The connection between these mechanical elements and chemical signaling processes is not known. Here, we show that α5β1 integrin switches between relaxed and tensioned states in response to myosin II–generated cytoskeletal force. Force combines with extracellular matrix stiffness to generate tension that triggers… 
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References

SHOWING 1-10 OF 24 REFERENCES
Force Required to Break α5β1Integrin-Fibronectin Bonds in Intact Adherent Cells Is Sensitive to Integrin Activation State*
TLDR
A model system is developed that characterizes the functional binding characteristic for adhesion receptors as the force required to separate the integrin-ligand bond and provides a basis for analysis of the functions of signaling and cytoskeletal elements in the adhesion process.
The mechanisms and dynamics of αvβ3 integrin clustering in living cells
TLDR
Fluorescence recovery after photobleaching analysis of Mn2+-induced integrin clusters revealed increased integrin turnover compared with mature focal contacts, whereas stabilization of the open conformation of the integrin ectodomain by mutagenesis reduced integrins turnover in focal contacts.
Focal adhesions as mechanosensors: a physical mechanism.
TLDR
A thermodynamic model for the mechanosensitivity of FA is proposed, according to which a molecular aggregate, subjected to pulling forces, tends to grow in the direction of force application by incorporating additional molecules.
Sensing the environment: a historical perspective on integrin signal transduction
TLDR
This historical perspective traces the key findings that have led to the current understanding of these important functions of integrins.
Synergistic roles for receptor occupancy and aggregation in integrin transmembrane function
TLDR
Combining antibody-mediated clustering with monovalent ligand occupancy induced accumulation of seven cytoskeletal proteins, thereby mimicking multivalent interactions with fibronectin or polyvalent peptides.
Rapid signal transduction in living cells is a unique feature of mechanotransduction
TLDR
Nanometer-scale cytoskeletal deformation analyses revealed that the strong activation sites of Src by stress colocalized with large deformation sites of microtubules, suggesting that micro Tubules are essential structures for transmitting stresses to activate cytoplasmic proteins.
A novel mode for integrin-mediated signaling: tethering is required for phosphorylation of FAK Y397.
TLDR
A kinetic model was established using HT1080 cells in which there was a linear relationship between the strength of adhesion, the proportion of alpha5beta1 integrin that could be chemically cross-linked, and the number of receptor-ligand bonds.
...
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