title: Characterisation of Drosophila thrombospondin defines an early origin of pentameric thrombospondins.
abstract: Thrombospondins (TSPs) are multidomain oligomers that have complex roles in cell interactions and tissue organisation. The five vertebrate TSPs comprise two subgroups, A and B, that are assembled as trimers or pentamers, respectively. An invertebrate TSP was recently discovered in Drosophila melanogaster, but there is no knowledge of the oligomerisation status or properties of this molecule. We developed by bioinformatics a new dataset containing the single TSP of Drosophila melanogaster and four other newly identified invertebrate TSPs to examine the phylogenetic relationships of TSPs. These analyses clearly indicate pentamerisation as an early attribute of TSPs. We demonstrate experimentally that D.melanogaster TSP is assembled as a pentamer, has heparin-binding activity and is a component of extracellular matrix (ECM). During embryogenesis, the TSP transcript is concentrated at muscle attachment sites and is expressed by a subset of myoblasts and in imaginal discs. These novel results establish TSPs as highly conserved ECM components in both invertebrates and vertebrates and open fresh perspectives on the conservation of structure and biological function within this family.
authors.affiliation: MRC Laboratory for Molecular Cell Biology and Department of Biochemistry and Molecular Biology, University College London, Gower St, London WC1E 6BT, UK. adamsj@ccf.org
authors.forename: Josephine C
authors.initials: JC
authors.lastname: Adams
authors.forename: Raymond
authors.initials: R
authors.lastname: Monk
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Taylor
authors.forename: Suat
authors.initials: S
authors.lastname: Ozbek
authors.forename: Nora
authors.initials: N
authors.lastname: Fascetti
authors.forename: Stefan
authors.initials: S
authors.lastname: Baumgartner
authors.forename: Juergen
authors.initials: J
authors.lastname: Engel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000235:genetics; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000737:chemistry* / Q000196:embryology / Q000235:genetics*; D019143:Evolution, Molecular; D005109:Extracellular Matrix / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006493:Heparin / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D010802:Phylogeny; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D019699:Thrombospondins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D019699:Thrombospondins; D006493:Heparin; D004247:DNA