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: Stefano Barbera, Luisa Raucci, Roberta Lugano, Gian Marco Tosi, Anna Dimberg, Annalisa Santucci, Federico Galvagni, Maurizio Orlandini
Formato: article
Lenguaje:EN
Publicado: MDPI AG 2021
Materias:
Src
Cbl
Crk
Acceso en línea:https://doaj.org/article/e6c7b607c7ed4b4281652e459054c523
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spelling oai:doaj.org-article:e6c7b607c7ed4b4281652e459054c5232021-11-25T17:56:27ZCD93 Signaling via Rho Proteins Drives Cytoskeletal Remodeling in Spreading Endothelial Cells10.3390/ijms2222124171422-00671661-6596https://doaj.org/article/e6c7b607c7ed4b4281652e459054c5232021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12417https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067During 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.Stefano BarberaLuisa RaucciRoberta LuganoGian Marco TosiAnna DimbergAnnalisa SantucciFederico GalvagniMaurizio OrlandiniMDPI AGarticleSrcCblCrkRac1Cdc42RhoABiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12417, p 12417 (2021)
institution DOAJ
collection DOAJ
language EN
topic Src
Cbl
Crk
Rac1
Cdc42
RhoA
Biology (General)
QH301-705.5
Chemistry
QD1-999
spellingShingle Src
Cbl
Crk
Rac1
Cdc42
RhoA
Biology (General)
QH301-705.5
Chemistry
QD1-999
Stefano Barbera
Luisa Raucci
Roberta Lugano
Gian Marco Tosi
Anna Dimberg
Annalisa Santucci
Federico Galvagni
Maurizio Orlandini
CD93 Signaling via Rho Proteins Drives Cytoskeletal Remodeling in Spreading Endothelial Cells
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.
format article
author Stefano Barbera
Luisa Raucci
Roberta Lugano
Gian Marco Tosi
Anna Dimberg
Annalisa Santucci
Federico Galvagni
Maurizio Orlandini
author_facet Stefano Barbera
Luisa Raucci
Roberta Lugano
Gian Marco Tosi
Anna Dimberg
Annalisa Santucci
Federico Galvagni
Maurizio Orlandini
author_sort Stefano Barbera
title 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_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_sort cd93 signaling via rho proteins drives cytoskeletal remodeling in spreading endothelial cells
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/e6c7b607c7ed4b4281652e459054c523
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