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Conformational states during vinculin unlocking differentially regulate focal adhesion properties.
Dror S Chorev1,2, Tova Volberg1, Ariel Livne1
1Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 7610001, Israel.
Scientific Reports
|February 11, 2018
Summary
Vinculin, a key protein in focal adhesions (FAs), transitions between auto-inhibited and active states. This study experimentally demonstrates this conformational change, revealing sequential steps that regulate FA growth and stability under mechanical stress.
Area of Science:
- Cell biology
- Biophysics
- Structural biology
Background:
- Focal adhesions (FAs) link the actin cytoskeleton to the extracellular matrix via integrins.
- FA regulation by mechanical stress is crucial, but molecular mechanisms of mechanosensing remain unclear.
- Vinculin, a focal adhesion protein, exists in auto-inhibited (closed) and active (open) conformations, potentially mediating mechanosensing.
Purpose of the Study:
- To experimentally demonstrate vinculin's conformational transition between closed and open states.
- To investigate the effects of this transition on focal adhesion structure and dynamics.
- To elucidate the sequential steps involved in vinculin's conformational change and their regulatory roles.
Main Methods:
- Multi-structural and biological approaches were employed.
- Probed the conformational transition of vinculin.
- Analyzed effects on focal adhesion structure and dynamics.
Main Results:
- Provided direct experimental evidence for vinculin's conformational transition from auto-inhibited to active states.
- Identified two sequential steps governing this transition.
- Demonstrated that these steps differentially regulate focal adhesion growth and stability.
Conclusions:
- The conformational transition of vinculin is experimentally validated.
- Vinculin's transition involves sequential steps that provide differential regulation of focal adhesion dynamics.
- Understanding vinculin's mechanosensitivity offers insights into focal adhesion regulation.
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