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Published on: October 13, 2019
CD93 Signaling via Rho Proteins Drives Cytoskeletal Remodeling in Spreading Endothelial Cells
Stefano Barbera1,2, Luisa Raucci1, Roberta Lugano2
1Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy.
Abstract:
During angiogenesis, cell adhesion molecules expressed on the endothelial cell surface promote the growth and survival of newly forming vessels. Hence, elucidation of the signaling pathways activated by cell-to-matrix adhesion may assist in the discovery of new targets to be used in antiangiogenic therapy. In proliferating endothelial cells, the single-pass transmembrane glycoprotein CD93 has recently emerged as an important endothelial cell adhesion molecule regulating vascular maturation. In this study, we unveil a signaling pathway triggered by CD93 that regulates actin cytoskeletal dynamics responsible of endothelial cell adhesion. We show that the Src-dependent phosphorylation of CD93 and the adaptor protein Cbl leads to the recruitment of Crk, which works as a downstream integrator in the CD93-mediated signaling. Moreover, confocal microscopy analysis of FRET-based biosensors shows that CD93 drives the coordinated activation of Rac1 and RhoA at the cell edge of spreading cells, thus promoting the establishment of cell polarity and adhesion required for cell motility.
Insights
This study reveals how CD93, an endothelial cell adhesion molecule, triggers signaling pathways that regulate cell adhesion and motility during blood vessel formation. Understanding this pathway offers potential targets for anti-angiogenic therapies.
Area of Science:
- Endothelial cell biology
- Molecular signaling pathways
- Angiogenesis research
Background:
- Cell adhesion molecules are crucial for blood vessel formation and maturation.
- CD93 is an endothelial cell adhesion molecule involved in vascular maturation.
- Understanding CD93 signaling may reveal targets for anti-angiogenic therapies.
Purpose of the Study:
- To elucidate the signaling pathway activated by CD93 in endothelial cells.
- To investigate CD93's role in regulating actin cytoskeletal dynamics and cell adhesion.
- To identify downstream effectors of CD93-mediated signaling.
Main Methods:
- Src-dependent phosphorylation assays.
- Co-immunoprecipitation to detect protein interactions.
- Confocal microscopy with FRET-based biosensors.
- Analysis of actin cytoskeletal dynamics and cell polarity.
Main Results:
- CD93 signaling involves Src-dependent phosphorylation of CD93 and Cbl.
- Crk acts as a downstream signaling integrator for CD93.
- CD93 promotes coordinated activation of Rac1 and RhoA at the cell edge.
- This activation establishes cell polarity and adhesion necessary for motility.
Conclusions:
- CD93 initiates a signaling cascade regulating endothelial cell adhesion and motility.
- The pathway involves CD93, Cbl, Crk, Rac1, and RhoA.
- This finding provides insights into vascular maturation and potential anti-angiogenic strategies.
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