CD93 and dystroglycan cooperation in human endothelial cell adhesion and migration
| Autor: | Federica Nardi, Maurizio Orlandini, Felice Petraglia, Annalisa Santucci, Federico Galvagni, Giulia Bernardini, Marco Maida, Silvia Vannuccini |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Proteomics
0301 basic medicine Cbl Endothelium Angiogenesis Biology Signal transduction 03 medical and health sciences Cell Movement Laminin Cell Adhesion Fluorescence Resonance Energy Transfer Human Umbilical Vein Endothelial Cells medicine Dystroglycan Animals Humans Electrophoresis Gel Two-Dimensional Phosphorylation Dystroglycans Cell adhesion Cells Cultured Mice Inbred BALB C Membrane Glycoproteins Microscopy Confocal C1qRp Src Oncology Capillaries Receptors Complement Endothelial stem cell Vascular endothelial growth factor A HEK293 Cells 030104 developmental biology medicine.anatomical_structure biology.protein Cancer research Tyrosine RNA Interference Research Paper Protein Binding |
| Zdroj: | Oncotarget |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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