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Secretion of VEGF-165 has unique characteristics, including shedding from the plasma membrane

Guzmán-Hernández, Maria Luisa
Balla, Tamas
Published in Molecular Biology of the Cell. 2014, vol. 25, no. 7, p. 1061-72
Abstract Vascular endothelial growth factor (VEGF) is a critical regulator of endothelial cell differentiation and vasculogenesis during both development and tumor vascularization. VEGF-165 is a major form that is secreted from the cells via a poorly characterized pathway. Here we use green fluorescent protein- and epitope-tagged VEGF-165 and find that its early trafficking between the endoplasmic reticulum and the Golgi requires the small GTP-binding proteins Sar1 and Arf1 and that its glycosylation in the Golgi compartment is necessary for efficient post-Golgi transport and secretion from the cells. The relative temperature insensitivity of VEGF secretion and its Sar1 and Arf1 inhibitory profiles distinguish it from other cargoes using the "constitutive" secretory pathway. Prominent features of VEGF secretion are the retention of the protein on the outer surface of the plasma membrane and the stimulation of its secretion by Ca(2+) and protein kinase C. Of importance, shedding of VEGF-165 from the cell surface together with other membrane components appears to be a unique feature by which some VEGF is delivered to the surroundings to exert its known biological actions. Understanding VEGF trafficking can reveal additional means by which tumor vascularization can be inhibited by pharmacological interventions.
Keywords AnimalsCOS CellsCell Membrane/drug effects/metabolism/ultrastructureCercopithecus aethiopsEndoplasmic Reticulum/drug effects/metabolismGTP Phosphohydrolases/metabolismGlycosylation/drug effectsGolgi Apparatus/drug effects/metabolismGreen Fluorescent Proteins/metabolismHuman Umbilical Vein Endothelial Cells/drug effects/metabolismHumansPhosphatidylinositol 4,5-Diphosphate/metabolismProtein Multimerization/drug effectsProtein Transport/drug effectsRecombinant Fusion Proteins/metabolismSirolimus/pharmacologyVascular Endothelial Growth Factor A/secretion/ultrastructure
PMID: 24501421
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Research group Progéniteurs neuronaux (141)
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GUZMÁN-HERNÁNDEZ, Maria Luisa et al. Secretion of VEGF-165 has unique characteristics, including shedding from the plasma membrane. In: Molecular Biology of the Cell, 2014, vol. 25, n° 7, p. 1061-72. https://archive-ouverte.unige.ch/unige:74474

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Deposited on : 2015-08-06

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