Annexin A8 promotes VEGF-A driven endothelial cell sprouting
| Autor: | Gonzalo Rosso, Nicole Heitzig, Victor Shahin, Ursula Rescher, Sophia N. Koerdt, Benjamin F. Brinkmann |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Vascular Endothelial Growth Factor A
0301 basic medicine Annexins Tetraspanins Angiogenesis Neovascularization Physiologic Review Biology Focal adhesion Extracellular matrix 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Tetraspanin Cell Adhesion Human Umbilical Vein Endothelial Cells Humans Neovascularization Pathologic Integrin beta1 Endothelial Cells Cell Biology Vascular Endothelial Growth Factor Receptor-2 Extracellular Matrix Cell biology Endothelial stem cell Vascular endothelial growth factor 030104 developmental biology chemistry Multiprotein Complexes 030220 oncology & carcinogenesis cardiovascular system Signal transduction Annexin A2 Signal Transduction |
| Zdroj: | Cell Adhesion & Migration. 11:275-287 |
| ISSN: | 1933-6926 1933-6918 |
| DOI: | 10.1080/19336918.2016.1264559 |
| Popis: | The physiological and pathological process of angiogenesis relies on orchestrated endothelial cell (EC) adhesion, migration and formation of new vessels. Here we report that human umbilical vein endothelial cells (HUVECs) deficient in Annexin A8 (AnxA8), a member of the annexin family of Ca2+- and membrane binding proteins, are strongly deficient in their ability to sprout in response to vascular endothelial growth factor (VEGF)-A, and are strongly impaired in their ability to migrate and adhere to β1 integrin-binding extracellular matrix (ECM) proteins. We find that these cells are defective in the formation of complexes containing the tetraspanin CD63, the main VEGF-A receptor VEGFR2, and the β1 integrin subunit, on the cell surface. We observe that upon VEGF-A activation of AnxA8-depleted HUVECs, VEGFR2 internalization is reduced, phosphorylation of VEGFR2 is increased, and the spatial distribution of Tyr577-phosphorylated focal adhesion kinase (pFAK577) is altered. We conclude that AnxA8 affects CD63/VEGFR2/β1 integrin complex formation, leading to hyperactivation of the VEGF-A signal transduction pathway, and severely disturbed VEGF-A-driven angiogenic sprouting. |
| Databáze: | OpenAIRE |
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