CD93 and dystroglycan cooperation in human endothelial cell adhesion and migration
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Federico Galvagni1,*, Federica Nardi1,*, Marco Maida1, Giulia Bernardini1, Silvia Vannuccini2, Felice Petraglia2, Annalisa Santucci1, Maurizio Orlandini1
1Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 2-53100 Siena, Italy
2Department of Molecular and Developmental Medicine, Obstetrics and Gynecology, University of Siena, 53100 Siena, Italy
*These authors contributed equally to this work
Maurizio Orlandini, e-mail: firstname.lastname@example.org
Keywords: angiogenesis, signal transduction, C1qRp, Src, Cbl
Received: June 29, 2015 Accepted: January 22, 2016 Published: February 02, 2016
CD93 is a transmembrane glycoprotein predominantly expressed in endothelial cells. Although CD93 displays proangiogenic activity, its molecular function in angiogenesis still needs to be clarified. To get molecular insight into the biological role of CD93 in the endothelium, we performed proteomic analyses to examine changes in the protein profile of endothelial cells after CD93 silencing. Among differentially expressed proteins, we identified dystroglycan, a laminin-binding protein involved in angiogenesis, whose expression is increased in vascular endothelial cells within malignant tumors. Using immunofluorescence, FRET, and proximity ligation analyses, we observed a close interaction between CD93 and β-dystroglycan. Moreover, silencing experiments showed that CD93 and dystroglycan promoted endothelial cell migration and organization into capillary-like structures. CD93 proved to be phosphorylated on tyrosine 628 and 644 following cell adhesion on laminin through dystroglycan. This phosphorylation was shown to be necessary for a proper endothelial migratory phenotype. Moreover, we showed that during cell spreading phosphorylated CD93 recruited the signaling protein Cbl, which in turn was phosphorylated on tyrosine 774. Altogether, our results identify a new signaling pathway which is activated by the cooperation between CD93 and dystroglycan and involved in the control of endothelial cell function.
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