Magic roundabout is a new member of the roundabout receptor family that is endothelial specific and expressed at sites of active angiogenesis.
We have used bioinformatic data mining to identify a novel, endothelial-specific gene encoding a protein with homology to the axon guidance protein roundabout (ROBO1). The new gene has been called magic roundabout (ROBO4; GenBank acc. no. AF361473) and is smaller than other members of the roundabout gene family. Thus, in the extracellular region, magic roundabout has only two of the five immunoglobulin and two of the three fibronectin domains present in other roundabout genes. Expression of magic roundabout in vitro was detected in only endothelial cells and was greater in cells exposed to hypoxia. In situ hybridization and immunohistochemistry validated the bioinformatic prediction that magic roundabout expression would be endothelial specific in vivo. Magic roundabout expression in the adult was restricted exclusively to sites of active angiogenesis, notably tumor vessels. The identification of magic roundabout shows that the roundabout gene family extends beyond neuronal tissue and that roundabout/slit interactions are likely to have a role in angiogenesis.
Huminiecki
Lukasz
L
Molecular Angiogenesis Laboratory, Cancer Research UK, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
Gorn
Michael
M
Suchting
Steven
S
Poulsom
Richard
R
Bicknell
Roy
R
D000595:Amino Acid Sequence; D004730:Endothelium, Vascular / Q000254:growth & development / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000235:genetics; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D000097905:Roundabout Proteins
D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; C462951:ROBO4 protein, human