Dynamin 2 regulation of integrin endocytosis, but not VEGF signaling, is crucial for developmental angiogenesis.
Here we show that dynamin 2 (Dnm2) is essential for angiogenesis in vitro and in vivo. In cultured endothelial cells lacking Dnm2, vascular endothelial growth factor (VEGF) signaling and receptor levels are augmented whereas cell migration and morphogenesis are impaired. Mechanistically, the loss of Dnm2 increases focal adhesion size and the surface levels of multiple integrins and reduces the activation state of β1 integrin. In vivo, the constitutive or inducible loss of Dnm2 in endothelium impairs branching morphogenesis and promotes the accumulation of β1 integrin at sites of failed angiogenic sprouting. Collectively, our data show that Dnm2 uncouples VEGF signaling from function and coordinates the endocytic turnover of integrins in a manner that is crucially important for angiogenesis in vitro and in vivo.
['Lee|Monica Y|MY|', 'Skoura|Athanasia|A|', 'Park|Eon Joo|EJ|', 'Landskroner-Eiger|Shira|S|', 'Jozsef|Levente|L|', 'Luciano|Amelia K|AK|', 'Murata|Takahisa|T|', 'Pasula|Satish|S|', 'Dong|Yunzhou|Y|', 'Bouaouina|Mohamed|M|', 'Calderwood|David A|DA|', 'Ferguson|Shawn M|SM|', 'De Camilli|Pietro|P|', 'Sessa|William C|WC|']
D000818:Animals D000831:Animals, Newborn D001808:Blood Vessels D002478:Cells, Cultured D034285:Dynamin II D004622:Embryo, Mammalian D004705:Endocytosis D005260:Female D061307:Human Umbilical Vein Endothelial Cells D006801:Humans D016023:Integrins D008297:Male D051379:Mice D008822:Mice, Transgenic D018919:Neovascularization, Physiologic D015398:Signal Transduction D042461:Vascular Endothelial Growth Factor A
Endocytosis Angiogenesis Endothelium Mouse