title: KIF13B regulates angiogenesis through Golgi to plasma membrane trafficking of VEGFR2.
abstract: Although the trafficking of newly synthesized VEGFR2 to the plasma membrane is a key determinant of angiogenesis, the molecular mechanisms of Golgi to plasma membrane trafficking are unknown. Here, we have identified a key role of the kinesin family plus-end molecular motor KIF13B in delivering VEGFR2 cargo from the Golgi to the endothelial cell surface. KIF13B is shown to interact directly with VEGFR2 on microtubules. We also observed that overexpression of truncated versions of KIF13B containing the binding domains that interact with VEGFR2 inhibited VEGF-induced capillary tube formation. KIF13B depletion prevented VEGF-mediated endothelial migration, capillary tube formation and neo-vascularization in mice. Impairment in trafficking induced by knockdown of KIF13B shunted VEGFR2 towards the lysosomal degradation pathway. Thus, KIF13B is an essential molecular motor required for the trafficking of VEGFR2 from the Golgi, and its delivery to the endothelial cell surface mediates angiogenesis.
authors.affiliation: Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USA Center of Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, IL 60612, USA.
authors.forename: Kaori H
authors.initials: KH
authors.lastname: Yamada
authors.affiliation: Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USA Center of Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, IL 60612, USA.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nakajima
authors.affiliation: Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USA Center of Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, IL 60612, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Geyer
authors.affiliation: Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USA Center of Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, IL 60612, USA.
authors.forename: Kishore K
authors.initials: KK
authors.lastname: Wary
authors.affiliation: Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USA.
authors.forename: Masuko
authors.initials: M
authors.lastname: Ushio-Fukai
authors.affiliation: Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USA Center of Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, IL 60612, USA.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Komarova
authors.affiliation: Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USA Center of Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, IL 60612, USA abmalik@uic.edu.
authors.forename: Asrar B
authors.initials: AB
authors.lastname: Malik
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008870:Microtubules / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics; D019076:Transgenes / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; C513406:KIF13B protein, human; D016547:Kinesins
keywords: Angiogenesis; Kinesin; Signal transduction; Trafficking; VEGFR2