title: Regulation of VEGF signaling by membrane traffic.
abstract: Recent findings have drawn attention to the role of membrane traffic in the signaling of vascular endothelial growth factor (VEGF). The significance of this development stems from the pivotal function of VEGF in vasculogenesis and angiogenesis. The outline of the regulation of VEGF receptor (VEGFR) signaling by membrane traffic is similar to that of the epidermal growth factor receptor (EGFR), a prototype of the intertwining between membrane traffic and signaling. There are, however, unique features in VEGFR signaling that are conferred in part by the involvement of the co-receptor neuropilin (Nrp). Nrp1 and VEGFR2 are integrated into membrane traffic through the adaptor protein synectin, which recruits myosin VI, a molecular motor that drives inward trafficking [17,21,64]. The recent detection of only mild vascular defects in a knockin mouse model that expresses Nrp1 lacking a cytoplasmic domain [104], questions the co-receptor's role in VEGF signaling and membrane traffic. The regulation of endocytosis by ephrin-B2 is another feature unique to VEGR2/3 [18,19], but it awaits a mechanistic explanation. Current models do not fully explain how membrane traffic bridges between VEGFR and the downstream effectors that produce its functional outcome, such as cell migration. VEGF-A appears to accomplish this task in part by recruiting endocytic vesicles carrying RhoA to internalized active VEGFR2 [58].
authors.affiliation: Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Lerner College of Medicine, 9500 Euclid Avenue, Cleveland, OH 44195, USA. horowia@ccf.org
authors.forename: Arie
authors.initials: A
authors.lastname: Horowitz
authors.forename: Himabindu Reddy
authors.initials: HR
authors.lastname: Seerapu
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D004705:Endocytosis; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D015398:Signal Transduction; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism*
chemical_list: D042442:Vascular Endothelial Growth Factors; D066246:ErbB Receptors