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Category CDBセミナー
Date and Time 2012-04-05 16:00 - 17:00
Venue Seminar Room A7F
Speaker Masanori Nakayama
Affiliation Max Planck Institute for Molecular Biomedicine, Department of Tisuue Morphogenesis
Title Spatial regulation of VEGF receptor endocytosis in angiogenesis
Poster click here to download(PDF)
Host Shinichi Nishikawa
Abstract Activities as diverse as migration, proliferation and patterning occur simultaneously and in a tightly coordinated fashion during tissue morphogenesis. In the growing vasculature, the formation of motile, invasive and filopodia-carrying endothelial sprouts needs to be balanced with the stabilization of existing, blood-transporting vessels. Here, I 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 VEGFR endocytosis and the activity of cell polarity proteins.
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