Logo: to the web site of Uppsala University

uu.sePublications from Uppsala University
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
The C-type lectin CD93 controls endothelial cell migration via activation of the Rho family of small GTPases
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab. Univ Siena, Dept Biotechnol Chem & Pharm, Via A Moro 2, I-53100 Siena, Italy..
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
Univ Siena, Dept Biotechnol Chem & Pharm, Via A Moro 2, I-53100 Siena, Italy..
Ctr Riferimento Oncol Aviano CRO IRCCS, Dept Res & Diag, Div Mol Oncol, Aviano, Italy..
Show others and affiliations
2021 (English)In: Matrix Biology, ISSN 0945-053X, E-ISSN 1569-1802, Vol. 99, p. 1-17Article in journal (Refereed) Published
Abstract [en]

Endothelial cell migration is essential to angiogenesis, enabling the outgrowth of new blood vessels both in physiological and pathological contexts. Migration requires the activation of several signaling pathways, the elucidation of which expands the opportunity to develop new drugs to be used in antiangiogenic therapy. In the proliferating endothelium, the interaction between the transmembrane glycoprotein CD93 and the extra cellular matrix activates signaling pathways that regulate cell adhesion, migration, and vascular maturation. Here we identify a pathway, comprising CD93, the adaptor proteins Cbl and Crk, and the small GTPases Rac1, Cdc42, and RhoA, which we propose acts as a regulator of cytoskeletal movements responsible for endothelial cell migration. In this framework, phosphorylation of Cbl on tyrosine 774 leads to the interaction with Crk, which acts as a downstream integrator in the CD93-mediated signaling regulating cell polarity and migration. Moreover, confocal microscopy analyses of GTPase biosensors show that CD93 drives coordinated activation of Rho-proteins at the cell edge of migratory endothelial cells. In conclusion, together with the demonstration of the key contribution of CD93 to the migratory process in living cells, these findings suggest that the signaling triggered by CD93 converges to the activation and modulation of the Rho GTPase signaling pathways regulating cell dynamics.

Place, publisher, year, edition, pages
ELSEVIER Elsevier, 2021. Vol. 99, p. 1-17
Keywords [en]
Cbl, Crk, Rac1, Cdc42, RhoA
National Category
Biochemistry and Molecular Biology Cell Biology
Identifiers
URN: urn:nbn:se:uu:diva-451598DOI: 10.1016/j.matbio.2021.05.006ISI: 000671579600001PubMedID: 34062268OAI: oai:DiVA.org:uu-451598DiVA, id: diva2:1588817
Funder
Swedish Cancer Society, CAN 2017/502Swedish Cancer Society, 20 1008 PjFSwedish Research Council, 2016-02495Swedish Research Council, 2020-02563Available from: 2021-08-30 Created: 2021-08-30 Last updated: 2024-01-15Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Authority records

Lugano, RobertaDimberg, Anna

Search in DiVA

By author/editor
Lugano, RobertaDimberg, Anna
By organisation
Department of Immunology, Genetics and PathologyScience for Life Laboratory, SciLifeLabVascular Biology
In the same journal
Matrix Biology
Biochemistry and Molecular BiologyCell Biology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 36 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf