Spatial regulation of VEGF receptor endocytosis in angiogenesis.
摘要：
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.
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关键词：
CELL-MIGRATION ENDOTHELIAL-CELLS POLARITY PROTEINS PAR COMPLEX TIP CELLS MORPHOGENESIS NOTCH POLARIZATION TRAFFICKING
DOI：
10.1038/ncb2679
被引量：
年份：
2013
Nature
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Nature
EBSCO
万方医学
掌桥科研
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