Proteomic Screen Identifies IGFBP7 as a Novel Component of Endothelial Cell-Specific Weibel-Palade Bodies
| Autor: | Ruben Bierings, I. Dienava-Verdoold, Astrid Kragt, Dorothee van Breevoort, Karine M. Valentijn, Jacqueline W.T.M. Klein Gebbinck, Jan Voorberg, Alexander B. Meijer, Jeroen Eikenboom, Ellen L. van Agtmaal, Anton J.G. Horrevoets, Bieuwke S. Dragt, Mar Fernandez-Borja |
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| Přispěvatelé: | Molecular cell biology and Immunology, ICaR - Ischemia and repair, Landsteiner Laboratory, Other departments |
| Rok vydání: | 2012 |
| Předmět: |
Proteomics
Agonist IGFBP7 Angiogenesis medicine.drug_class proteome Genetic Vectors Neovascularization Physiologic Biology Transfection Biochemistry Exocytosis Mass Spectrometry Vascular lumen angiogenesis von Willebrand Factor Organelle Human Umbilical Vein Endothelial Cells Weibel–Palade body medicine Humans Weibel-Palade bodies General Chemistry Immunohistochemistry endothelial cells Protein Structure Tertiary Cell biology Insulin-Like Growth Factor Binding Proteins Endothelial stem cell P-Selectin Protein Transport HEK293 Cells Immunology Proteome |
| Zdroj: | Journal of Proteome Research, 11(5), 2925-2936. American Chemical Society van Breevoort, D, van Agtmaal, E L, Dragt, B S, Gebbinck, J K, Dienava-Verdoold, I, Kragt, A, Bierings, R, Horrevoets, A J G, Valentijn, K M, Eikenboom, J C, Fernandez-Borja, M, Meijer, A B & Voorberg, J 2012, ' Proteomic Screen Identifies IGFBP7 as a Novel Component of Endothelial Cell-Specific Weibel-Palade Bodies ', Journal of Proteome Research, vol. 11, no. 5, pp. 2925-2936 . https://doi.org/10.1021/pr300010r Journal of proteome research, 11(5), 2925-2936. American Chemical Society Journal of Proteome Research, 11(5), 2925-2936 |
| ISSN: | 1535-3893 |
| Popis: | Vascular endothelial cells contain unique storage organelles, designated Weibel-Palade bodies (WPBs), that deliver inflammatory and hemostatic mediators to the vascular lumen in response to agonists like thrombin and vasopressin. The main component of WPBs is von Willebrand factor (VWF), a multimeric glycoprotein crucial for platelet plug formation. In addition to VWF, several other components are known to be stored in WPBs, like osteoprotegerin, monocyte chemoattractant protein-1 and angiopoetin-2 (Ang-2). Here, we used an unbiased proteomics approach to identify additional residents of WPBs. Mass spectrometry analysis of purified WPBs revealed the presence of several known components such as VWF, Ang-2, and P-selectin. Thirty-five novel candidate WPB residents were identified that included insulin-like growth factor binding protein-7 (IGFBP7), which has been proposed to regulate angiogenesis. Immunocytochemistry revealed that IGFBP7 is a bona fide WPB component. Cotransfection studies showed that IGFBP7 trafficked to pseudo-WPB in HEK293 cells. Using a series of deletion variants of VWF, we showed that targeting of IGFBP7 to pseudo-WPBs was dependent on the carboxy-terminal D4-C1-C2-C3-CK domains of VWF. IGFBP7 remained attached to ultralarge VWF strings released upon exocytosis of WPBs under flow. The presence of IGFBP7 in WPBs highlights the role of this subcellular compartment in regulation of angiogenesis. |
| Databáze: | OpenAIRE |
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