title: CD93 and dystroglycan cooperation in human endothelial cell adhesion and migration adhesion and migration.
abstract: 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.
authors: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy.
authors: Federico
authors: F
authors: Galvagni
authors: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy.
authors: Federica
authors: F
authors: Nardi
authors: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy.
authors: Marco
authors: M
authors: Maida
authors: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy.
authors: Giulia
authors: G
authors: Bernardini
authors: Department of Molecular and Developmental Medicine, Obstetrics and Gynecology, University of Siena, 53100 Siena, Italy.
authors: Silvia
authors: S
authors: Vannuccini
authors: Department of Molecular and Developmental Medicine, Obstetrics and Gynecology, University of Siena, 53100 Siena, Italy.
authors: Felice
authors: F
authors: Petraglia
authors: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy.
authors: Annalisa
authors: A
authors: Santucci
authors: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy.
authors: Maurizio
authors: M
authors: Orlandini
mesh_terms: D000818:Animals; D002196:Capillaries / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D049030:Dystroglycans / Q000235:genetics / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D031541:Fluorescence Resonance Energy Transfer; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D010766:Phosphorylation; D011485:Protein Binding; D040901:Proteomics / Q000379:methods; D034622:RNA Interference; D011951:Receptors, Complement / Q000235:genetics / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D007797:Laminin; D008562:Membrane Glycoproteins; D011951:Receptors, Complement; C032402:complement 1q receptor; D049030:Dystroglycans; D014443:Tyrosine
keywords: C1qRp; Cbl; Src; angiogenesis; signal transduction