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Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Development 2014 ; 141 (7): 1465-72 Nephropedia Template TP
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Dynamin 2 regulation of integrin endocytosis, but not VEGF signaling, is crucial for developmental angiogenesis #MMPMID24598168
Lee MY; Skoura A; Park EJ; Landskroner-Eiger S; Jozsef L; Luciano AK; Murata T; Pasula S; Dong Y; Bouaouina M; Calderwood DA; Ferguson SM; De Camilli P; Sessa WC
Development 2014[Apr]; 141 (7): 1465-72 PMID24598168show ga
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 ?1 integrin. In vivo, the constitutive or inducible loss of Dnm2 in endothelium impairs branching morphogenesis and promotes the accumulation of ?1 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.