title: Dynamin 2 regulation of integrin endocytosis, but not VEGF signaling, is crucial for developmental angiogenesis.
abstract: 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.
authors.affiliation: Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Monica Y
authors.initials: MY
authors.lastname: Lee
authors.forename: Athanasia
authors.initials: A
authors.lastname: Skoura
authors.forename: Eon Joo
authors.initials: EJ
authors.lastname: Park
authors.forename: Shira
authors.initials: S
authors.lastname: Landskroner-Eiger
authors.forename: Levente
authors.initials: L
authors.lastname: Jozsef
authors.forename: Amelia K
authors.initials: AK
authors.lastname: Luciano
authors.forename: Takahisa
authors.initials: T
authors.lastname: Murata
authors.forename: Satish
authors.initials: S
authors.lastname: Pasula
authors.forename: Yunzhou
authors.initials: Y
authors.lastname: Dong
authors.forename: Mohamed
authors.initials: M
authors.lastname: Bouaouina
authors.forename: David A
authors.initials: DA
authors.lastname: Calderwood
authors.forename: Shawn M
authors.initials: SM
authors.lastname: Ferguson
authors.forename: Pietro
authors.initials: P
authors.lastname: De Camilli
authors.forename: William C
authors.initials: WC
authors.lastname: Sessa
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001808:Blood Vessels / Q000196:embryology* / Q000254:growth & development; D002478:Cells, Cultured; D034285:Dynamin II / Q000235:genetics / Q000502:physiology*; D004622:Embryo, Mammalian; D004705:Endocytosis / Q000235:genetics*; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*
chemical_list: D016023:Integrins; D042461:Vascular Endothelial Growth Factor A; D034285:Dynamin II
keywords: Angiogenesis; Endocytosis; Endothelium; Mouse