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CD93 Signaling via Rho Proteins Drives Cytoskeletal Remodeling in Spreading Endothelial Cells

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 t...

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Autores principales: Barbera, Stefano, Raucci, Luisa, Lugano, Roberta, Tosi, Gian Marco, Dimberg, Anna, Santucci, Annalisa, Galvagni, Federico, Orlandini, Maurizio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8622518/
https://www.ncbi.nlm.nih.gov/pubmed/34830297
http://dx.doi.org/10.3390/ijms222212417
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author Barbera, Stefano
Raucci, Luisa
Lugano, Roberta
Tosi, Gian Marco
Dimberg, Anna
Santucci, Annalisa
Galvagni, Federico
Orlandini, Maurizio
author_facet Barbera, Stefano
Raucci, Luisa
Lugano, Roberta
Tosi, Gian Marco
Dimberg, Anna
Santucci, Annalisa
Galvagni, Federico
Orlandini, Maurizio
author_sort Barbera, Stefano
collection PubMed
description 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.
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spelling pubmed-86225182021-11-27 CD93 Signaling via Rho Proteins Drives Cytoskeletal Remodeling in Spreading Endothelial Cells Barbera, Stefano Raucci, Luisa Lugano, Roberta Tosi, Gian Marco Dimberg, Anna Santucci, Annalisa Galvagni, Federico Orlandini, Maurizio Int J Mol Sci Article 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. MDPI 2021-11-17 /pmc/articles/PMC8622518/ /pubmed/34830297 http://dx.doi.org/10.3390/ijms222212417 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Barbera, Stefano
Raucci, Luisa
Lugano, Roberta
Tosi, Gian Marco
Dimberg, Anna
Santucci, Annalisa
Galvagni, Federico
Orlandini, Maurizio
CD93 Signaling via Rho Proteins Drives Cytoskeletal Remodeling in Spreading Endothelial Cells
title CD93 Signaling via Rho Proteins Drives Cytoskeletal Remodeling in Spreading Endothelial Cells
title_full CD93 Signaling via Rho Proteins Drives Cytoskeletal Remodeling in Spreading Endothelial Cells
title_fullStr CD93 Signaling via Rho Proteins Drives Cytoskeletal Remodeling in Spreading Endothelial Cells
title_full_unstemmed CD93 Signaling via Rho Proteins Drives Cytoskeletal Remodeling in Spreading Endothelial Cells
title_short CD93 Signaling via Rho Proteins Drives Cytoskeletal Remodeling in Spreading Endothelial Cells
title_sort cd93 signaling via rho proteins drives cytoskeletal remodeling in spreading endothelial cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8622518/
https://www.ncbi.nlm.nih.gov/pubmed/34830297
http://dx.doi.org/10.3390/ijms222212417
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