Identification of a receptor necessary for Nogo-B stimulated chemotaxis and morphogenesis of endothelial cells.
Nogo isoforms (Nogo-A and -B) have been implicated in regulating neural and cardiovascular functions, such as cell spreading and chemotaxis. Unlike the loop domain (Nogo-66) found in all Nogo isoforms that can interact with a neural-specific Nogo-66 receptor, the receptor for the amino terminus of Nogo-B that mediates vascular function is unknown. Here, we identify a previously uncharacterized Nogo-B receptor specific for the amino terminus of Nogo-B and show that Nogo-B receptor localizes with the ligand Nogo-B during VEGF and wound healing angiogenesis in vivo, mediates chemotaxis in a heterologous expression system and chemotaxis, and 3D tube formation in native endothelial cells. Thus, identification of this receptor may lead to the discovery of agonists or antagonists of this pathway to regulate vascular remodeling and angiogenesis.
Miao
Robert Qing
RQ
Department of Pharmacology and Vascular Cell Signaling and Therapeutics Program, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06536, USA.
Gao
Yuan
Y
Harrison
Kenneth D
KD
Prendergast
Jay
J
Acevedo
Lisette M
LM
Yu
Jun
J
Hu
Fenghua
F
Strittmatter
Stephen M
SM
Sessa
William C
WC
D000595:Amino Acid Sequence; D000818:Animals; D048430:Cell Shape; D002478:Cells, Cultured; D002633:Chemotaxis; D002522:Chlorocebus aethiops; D006224:Cricetinae; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000070798:Nogo Proteins; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*
D009185:Myelin Proteins; C512614:NUS1 protein, human; D000070798:Nogo Proteins; C512615:Nogo-B receptor, mouse; D020033:Protein Isoforms; C000603199:RTN4 protein, human; D011956:Receptors, Cell Surface; C000603201:Rtn4 protein, mouse