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

Maria Luisa Guzmán-Hernández, Gael Potter, Kristòf Egervári, J. Kiss, Tamas Balla

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 Ca2+ 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.

Original languageEnglish
Pages (from-to)1061-1072
Number of pages12
JournalMolecular Biology of the Cell
Volume25
Issue number7
DOIs
Publication statusPublished - Apr 1 2014

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Vascular Endothelial Growth Factor A
Cell Membrane
Secretory Pathway
Green Fluorescent Proteins
Glycosylation
GTP-Binding Proteins
Endoplasmic Reticulum
Protein Kinase C
Epitopes
Cell Differentiation
Neoplasms
Endothelial Cells
human VEGFA protein
Pharmacology
Temperature
Membranes
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology
  • Medicine(all)

Cite this

Secretion of VEGF-165 has unique characteristics, including shedding from the plasma membrane. / Guzmán-Hernández, Maria Luisa; Potter, Gael; Egervári, Kristòf; Kiss, J.; Balla, Tamas.

In: Molecular Biology of the Cell, Vol. 25, No. 7, 01.04.2014, p. 1061-1072.

Research output: Contribution to journalArticle

Guzmán-Hernández, Maria Luisa ; Potter, Gael ; Egervári, Kristòf ; Kiss, J. ; Balla, Tamas. / Secretion of VEGF-165 has unique characteristics, including shedding from the plasma membrane. In: Molecular Biology of the Cell. 2014 ; Vol. 25, No. 7. pp. 1061-1072.
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