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Updated: Jul 20, 2025
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The Assembly and Application of 'Shear Rings': A Novel Endothelial Model for Orbital, Unidirectional and Periodic Fluid Flow and Shear Stress
Published on: October 31, 2016
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Serine phosphorylation of the RhoGEF Trio stabilizes endothelial cell-cell junctions.
Anna E Daniel1, Werner J van der Meer2, Lynn Wester1
1Department of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Small Gtpases
|August 2, 2023
Summary
Phosphorylation of the RhoGEF Trio protein at serine residues S1785/S1786 enhances its localization to cell junctions. This improves endothelial cell-cell junction stability, particularly in response to thrombin.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The RhoGEF Trio protein is crucial for various cellular processes, including cell migration and junction stability.
- The precise mechanisms regulating Trio activation and its role in endothelial cell junctions remain largely unknown.
Purpose of the Study:
- To investigate the phosphorylation sites on Trio and their functional consequences.
- To elucidate the role of Trio phosphorylation in endothelial cell-cell junction stability.
Main Methods:
- Stable isotope labeling by amino acids in cell culture (SILAC)-based mass spectrometry to identify phosphorylation sites.
- Site-directed mutagenesis to create phosphomimetic Trio mutants (S1785D/S1786D).
- Analysis of Trio localization and endothelial cell-cell junction stability upon thrombin stimulation.
Main Results:
- Two serine residues (S1785/S1786) in Trio were identified as highly phosphorylated upon thrombin treatment.
- Phosphomimetic Trio mutants did not show increased Rac1/RhoG exchange activity.
- Trio mutants exhibited enhanced localization at cell-cell junctions and prevented thrombin-induced junction destabilization.
Conclusions:
- Serine phosphorylation of Trio potentiates its localization to junctional regions.
- This enhanced localization promotes local Rac1 exchange and increases endothelial cell-cell junction stability.
- Trio phosphorylation plays a key role in maintaining endothelial barrier function.
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