title: A family of proteins related to Spätzle, the toll receptor ligand, are encoded in the Drosophila genome.
abstract: The Drosophila gene Spätzle encodes the activating ligand for the Toll receptor. This signaling pathway is required for dorso-ventral patterning in the early embryo and an antifungal immune response in larvae and adults. The genome sequence of Drosophila shows that there are a total of eight Toll-like receptors and these may function in other aspects of embryonic development and innate immunity. Here we describe five Drosophila homologues of Spätzle (Spz2-6) found using an iterative searching method. All five appear to encode proteins containing neurotrophin-like cystine-knot domains. In addition, most retain a characteristic intron-exon structure shared with the prototype Spätzle gene. This provides evidence that the family arose by ancient gene duplication events and indicates that the gene products may represent activating ligands for corresponding Toll receptors. Expression studies show that only Spz4 is expressed strongly in larvae and adults and thus may be involved in an ancillary antifungal response mediated by Toll-5. By contrast, Spz6 shows a complex spatial and temporally regulated expression pattern in the late embryo. Thus the new Toll/Spätzle families of signaling molecules may have important roles in other aspects of development and immunity.
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: J S
authors.initials: JS
authors.lastname: Parker
authors.forename: K
authors.initials: K
authors.lastname: Mizuguchi
authors.forename: N J
authors.initials: NJ
authors.lastname: Gay
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D019992:Databases as Topic; D004330:Drosophila / Q000196:embryology / Q000235:genetics* / Q000254:growth & development; D029721:Drosophila Proteins; D020224:Expressed Sequence Tags; D018507:Gene Expression Regulation, Developmental; D016678:Genome; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D007438:Introns; D007814:Larva / Q000378:metabolism; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D016366:Open Reading Frames / Q000235:genetics; D010802:Phylogeny; D011487:Protein Conformation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D016415:Sequence Alignment; D015398:Signal Transduction; D051198:Toll-Like Receptor 5; D051193:Toll-Like Receptors
chemical_list: D029721:Drosophila Proteins; D019476:Insect Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D051198:Toll-Like Receptor 5; D051193:Toll-Like Receptors; C086179:spz protein, Drosophila; C495341:tehao protein, Drosophila