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Dynamic alterations in decoy VEGF receptor-1 stability regulate angiogenesis
- Source :
- Nature Communications, Nature Communications, Vol 8, Iss 1, Pp 1-15 (2017)
- Publication Year :
- 2017
- Publisher :
- Nature Publishing Group, 2017.
-
Abstract
- Blood vessel expansion is driven by sprouting angiogenesis of endothelial cells, and is essential for development, wound healing and disease. Membrane-localized vascular endothelial growth factor receptor-1 (mVEGFR1) is an endothelial cell-intrinsic decoy receptor that negatively modulates blood vessel morphogenesis. Here we show that dynamic regulation of mVEGFR1 stability and turnover in blood vessels impacts angiogenesis. mVEGFR1 is highly stable and constitutively internalizes from the plasma membrane. Post-translational palmitoylation of mVEGFR1 is a binary stabilization switch, and ligand engagement leads to depalmitoylation and lysosomal degradation. Trafficking of palmitoylation enzymes via Rab27a regulates mVEGFR1 stability, as reduced levels of Rab27a impaired palmitoylation of mVEGFR1, decreased its stability, and elevated blood vessel sprouting and in vivo angiogenesis. These findings identify a regulatory axis affecting blood vessel morphogenesis that highlights exquisite post-translational regulation of mVEGFR1 in its role as a molecular rheostat.<br />Membrane-bound mVEGFR1 is a decoy VEGF-A receptor that regulates VEGF-A signalling amplitude. Boucher et al. show that Rab27a-regulated palmitoylation of mVEGFR1 redirects the receptor from a stable, constitutively recycling mode to a degradative route that removes ligands from the system.
- Subjects :
- 0301 basic medicine
Male
Vascular Endothelial Growth Factor A
Angiogenesis
General Physics and Astronomy
Blood vessel morphogenesis
Ligands
rab27 GTP-Binding Proteins
Neovascularization
chemistry.chemical_compound
Mice
0302 clinical medicine
Cell Movement
Mice, Inbred C3H
Multidisciplinary
Neovascularization, Pathologic
Gene Expression Regulation, Developmental
Cell biology
Vascular endothelial growth factor
Vascular endothelial growth factor A
Protein Transport
medicine.anatomical_structure
Female
medicine.symptom
Blood vessel
Signal Transduction
Science
Lipoylation
Neovascularization, Physiologic
Biology
Models, Biological
General Biochemistry, Genetics and Molecular Biology
Article
03 medical and health sciences
Palmitoylation
medicine
Human Umbilical Vein Endothelial Cells
Animals
Humans
Sprouting angiogenesis
Wound Healing
Vascular Endothelial Growth Factor Receptor-1
Cell Membrane
Endothelial Cells
Epistasis, Genetic
General Chemistry
030104 developmental biology
chemistry
Blood Vessels
Protein Processing, Post-Translational
030217 neurology & neurosurgery
Acyltransferases
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....28f1ecc72fd575428bee9a93be8eb27f