VEGFR1 (Flt1) regulates Rab4 recycling to control fibronectin polymerization and endothelial vessel branching
| Autor: | Alexandra Gampel, Patrick T. Caswell, Simon T. Barry, Jim C. Norman, Matthew Jones, Marnie S. Roberts, Harry Mellor, Kim Moran-Jones |
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| Rok vydání: | 2009 |
| Předmět: |
animal structures
Endosome Angiogenesis Integrin Cell Endocytosis Biochemistry Biopolymers Structural Biology Genetics medicine Humans Receptor Molecular Biology Cells Cultured Vascular Endothelial Growth Factor Receptor-1 biology Effector rab4 GTP-Binding Proteins Cell Biology Cell biology Fibronectins Fibronectin medicine.anatomical_structure cardiovascular system biology.protein Endothelium Vascular |
| Zdroj: | Traffic (Copenhagen, Denmark). 10(6) |
| ISSN: | 1600-0854 |
| Popis: | The cell's main receptor for VEGF, VEGFR2 (Kdr) is one of the most important positive regulators of new blood vessel growth and its downstream signalling is well characterized. By contrast, VEGFR1 (Flt1) and the mechanisms by which this VEGF receptor promotes branching morphogenesis in angiogenesis remain relatively unclear.Here we report that engagement of VEGFR1 activates a Rab4A-dependent pathway that transports alphavbeta3 Integrin from early endosomes to the plasma membrane, and that this is required for VEGF-driven fibronectin polymerization in endothelial cells. Furthermore, VEGFR1 acts to promote endothelial tubule branching in an organotypic model of angiogenesis via a mechanism that requires Rab4A and alphavbeta3 Integrin. We conclude that a recycling pathway regulated by Rab4A is a critical effector of VEGFR1 during branching morphogenesis of the vasculature. |
| Databáze: | OpenAIRE |
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