RGD Reference Report - Spatial regulation of VEGF receptor endocytosis in angiogenesis. - Rat Genome Database

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Spatial regulation of VEGF receptor endocytosis in angiogenesis.

Authors: Nakayama, Masanori  Nakayama, Akiko  van Lessen, Max  Yamamoto, Hiroyuki  Hoffmann, Sarah  Drexler, Hannes C A  Itoh, Norimichi  Hirose, Tomonori  Breier, Georg  Vestweber, Dietmar  Cooper, Jonathan A  Ohno, Shigeo  Kaibuchi, Kozo  Adams, Ralf H 
Citation: Nakayama M, etal., Nat Cell Biol. 2013 Mar;15(3):249-60. doi: 10.1038/ncb2679. Epub 2013 Jan 27.
RGD ID: 13432247
Pubmed: PMID:23354168   (View Abstract at PubMed)
PMCID: PMC3901019   (View Article at PubMed Central)
DOI: DOI:10.1038/ncb2679   (Journal Full-text)

Activities as diverse as migration, proliferation and patterning occur simultaneously and in a coordinated fashion during tissue morphogenesis. In the growing vasculature, the formation of motile, invasive and filopodia-carrying endothelial sprouts is balanced with the stabilization of blood-transporting vessels. Here, we show that sprouting endothelial cells in the retina have high rates of VEGF uptake, VEGF receptor endocytosis and turnover. These internalization processes are opposed by atypical protein kinase C activity in more stable and mature vessels. aPKC phosphorylates Dab2, a clathrin-associated sorting protein that, together with the transmembrane protein ephrin-B2 and the cell polarity regulator PAR-3, enables VEGF receptor endocytosis and downstream signal transduction. Accordingly, VEGF receptor internalization and the angiogenic growth of vascular beds are defective in loss-of-function mice lacking key components of this regulatory pathway. Our work uncovers how vessel growth is dynamically controlled by local VEGF receptor endocytosis and the activity of cell polarity proteins.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding enablesIPIUniProtKB:P5280013432247PMID:23354168IntAct 

Objects Annotated

Genes (Rattus norvegicus)
Dab2  (DAB adaptor protein 2)


Additional Information