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srGAP2 deactivates RhoA to control the duration of thrombin-mediated endothelial permeability
Alba Lopez Rioja1, Ashton Faulkner1, Harry Mellor1
1School of Biochemistry, Biomedical Sciences Building, University of Bristol, Bristol, UK.
Vascular Biology (Bristol, England)
|April 20, 2022
Summary
The protein srGAP2 limits endothelial barrier opening caused by inflammatory mediators like thrombin. It helps cells reform the barrier by switching off RhoA signaling after contraction.
Area of Science:
- Endothelial biology
- Cell signaling
- Vascular permeability
Background:
- The endothelial barrier controls substance exchange between blood and tissues.
- Inflammatory mediators, such as thrombin, disrupt this barrier by opening cell junctions.
- This disruption allows plasma proteins and leukocytes to extravasate into tissues.
Observation:
- The protein SLIT-ROBO Rho GTPase-activating protein 2 (srGAP2) was investigated for its role in endothelial barrier regulation.
- srGAP2 is not essential for barrier function in resting endothelial cells.
- Depletion of srGAP2 significantly amplifies and prolongs thrombin-induced junctional opening.
Findings:
- srGAP2 regulates the magnitude and duration of endothelial barrier opening.
- It switches off RhoA signaling post-contraction, enabling cell resealing and barrier reformation.
- srGAP2 is crucial for restoring barrier integrity after activation by thrombin, TNFα, and angiotensin II.
Implications:
- srGAP2 plays a general role in controlling RhoA signaling in endothelial permeability.
- It acts as a key regulator, limiting barrier opening and promoting resealing.
- Understanding srGAP2's function could lead to new therapeutic strategies for inflammatory conditions affecting vascular integrity.
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