Dynamic alterations in decoy VEGF receptor-1 stability regulate angiogenesis

Joshua M. Boucher, Ryan P. Clark, Diana C. Chong, Kathryn M. Citrin, Lyndsay A. Wylie and Victoria L. Bautch ()
Additional contact information
Joshua M. Boucher: University of North Carolina at Chapel Hill
Ryan P. Clark: University of North Carolina at Chapel Hill
Diana C. Chong: Genetics and Molecular Biology Curriculum, University of North Carolina at Chapel Hill
Kathryn M. Citrin: University of North Carolina at Chapel Hill
Lyndsay A. Wylie: Genetics and Molecular Biology Curriculum, University of North Carolina at Chapel Hill
Victoria L. Bautch: University of North Carolina at Chapel Hill

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: 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.

Date: 2017
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms15699 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15699

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms15699

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().