title: Ninein is expressed in the cytoplasm of angiogenic tip-cells and regulates tubular morphogenesis of endothelial cells.
abstract: OBJECTIVE
  Angiogenesis is an integral part of many physiological processes but may also aggravate pathological conditions such as cancer. Development of effective angiogenesis inhibitors requires a thorough understanding of the molecular mechanisms regulating vessel formation. The aim of this project was to identify proteins that regulate tubular morphogenesis of endothelial cells.
  
  
  RESULTS
  Phosphotyrosine-dependent affinity-purification and mass spectrometry showed tyrosine phosphorylation of ninein during tubular morphogenesis of endothelial cells. Ninein was recently identified as a centrosomal microtubule-anchoring protein. Our results show that ninein is localized in the cytoplasm in endothelial cells, and that it is highly expressed in the vasculature in normal and pathological human tissues. Using embryoid bodies as a model of vascular development, we found that ninein is abundantly expressed in the cytoplasm of endothelial cells during sprouting angiogenesis, in particular in the sprouting tip-cell. In accordance, siRNA-dependent silencing of ninein in endothelial cells inhibited tubular morphogenesis.
  
  
  CONCLUSIONS
  In this study, we show that ninein is expressed in developing vessels and in endothelial tip cells, and that ninein is critical for formation of the vascular tube. These data strongly implicate ninein as an important new regulator of angiogenesis.
authors.affiliation: Department of Genetics and Pathology, Rudbeck Laboratory, S-751 85 Uppsala, Sweden.
authors.forename: Taro
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Petter
authors.initials: P
authors.lastname: Schiller
authors.forename: Lothar C
authors.initials: LC
authors.lastname: Dieterich
authors.forename: Fuad
authors.initials: F
authors.lastname: Bahram
authors.forename: Yuji
authors.initials: Y
authors.lastname: Iribe
authors.forename: Ulf
authors.initials: U
authors.lastname: Hellman
authors.forename: Charlotte
authors.initials: C
authors.lastname: Wikner
authors.forename: Gordon
authors.initials: G
authors.lastname: Chan
authors.forename: Lena
authors.initials: L
authors.lastname: Claesson-Welsh
authors.forename: Anna
authors.initials: A
authors.lastname: Dimberg
mesh_terms: D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002478:Cells, Cultured; D003593:Cytoplasm / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008955:Models, Cardiovascular; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013552:Swine; D014162:Transfection
chemical_list: D003598:Cytoskeletal Proteins; C512806:NIN protein, human; C099035:Nin protein, mouse; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D016222:Fibroblast Growth Factor 2