Dynamic alterations in decoy VEGF receptor-1 stability regulate angiogenesis.

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Boucher JM,Clark RP,Chong DC,Citrin KM,Wylie LA,Bautch VL

doi

10.1038/ncomms15699

subject

Has Abstract

pub_date

2017-06-07 00:00:00

pages

15699

issn

2041-1723

pii

ncomms15699

journal_volume

8

pub_type

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