title: Matrix-mediated canal formation in primmorphs from the sponge Suberites domuncula involves the expression of a CD36 receptor-ligand system.
abstract: Sponges (Porifera), represent the phylogenetically oldest metazoan phylum still extant today. Recently, molecular biological studies provided compelling evidence that these animals share basic receptor/ligand systems, especially those involved in bodyplan formation and in immune recognition, with the higher metazoan phyla. An in vitro cell/organ-like culture system, the primmorphs, has been established that consists of proliferating and differentiating cells, but no canals of the aquiferous system. We show that after the transfer of primmorphs from the demosponge Suberites domuncula to a homologous matrix (galectin), canal-like structures are formed in these 3D-cell aggregates. In parallel with the formation of these structures a gene is expressed whose deduced protein falls into the CD36/LIMPII receptor family. The receptor was cloned and found to be strongly expressed after adhesion to the galectin matrix. This process was suppressed if primmorphs were co-incubated with a homologous polypeptide containing the CSVTCG domain, as found in thrombospondin-1 (and related) molecules of vertebrates. In situ hybridization studies revealed that the S. domuncula CD36/LIMPII receptor is localized in the pinacocytes that surround the canals of the sponge. Furthermore, a secondary metabolite from a sponge-associated bacterium was isolated and characterized, the 2-methylthio-1,4-naphthoquinone (MTN). MTN causes inhibition of cell proliferation of vertebrate tumor cells at concentrations of >80 ng/ml. However, doses of only 2 ng are required to potently inhibit angiogenesis in the chick chorio-allantoic membrane assay. At concentrations of 10 ng/ml this compound was also found to suppress the expression of the S. domuncula CD36/LIMPII; this result is a first indication that this secondary metabolite has a conserved functional activity: the suppression of the formation of the circulation system, from sponges to vertebrates.
authors.affiliation: Institut für Physiologische Chemie und Pathobiochemie, Abteilung Angewandte Molekularbiologie, Johannes Gutenberg-Universität Mainz, 55099 Mainz, Germany. wmueller@mail.uni-mainz.de
authors.forename: Werner E G
authors.initials: WE
authors.lastname: Müller
authors.forename: Narsinh L
authors.initials: NL
authors.lastname: Thakur
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ushijima
authors.forename: Archana N
authors.initials: AN
authors.lastname: Thakur
authors.forename: Anatoli
authors.initials: A
authors.lastname: Krasko
authors.forename: Gaël
authors.initials: G
authors.lastname: Le Pennec
authors.forename: Madhavi M
authors.initials: MM
authors.lastname: Indap
authors.forename: Sanja
authors.initials: S
authors.lastname: Perovic-Ottstadt
authors.forename: Heinz C
authors.initials: HC
authors.lastname: Schröder
authors.forename: Gerhard
authors.initials: G
authors.lastname: Lang
authors.forename: Gerhard
authors.initials: G
authors.lastname: Bringmann
mesh_terms: D000482:Allantois / Q000187:drug effects; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D018955:CD36 Antigens / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002449:Cell Aggregation; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D002823:Chorion / Q000187:drug effects; D003001:Cloning, Molecular; D004305:Dose-Response Relationship, Drug; D019143:Evolution, Molecular; D005109:Extracellular Matrix / Q000378:metabolism*; D037161:Galectins / Q000138:chemical synthesis / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005982:Glutathione Transferase / Q000378:metabolism; D008024:Ligands; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009285:Naphthoquinones / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D010802:Phylogeny; D011161:Porifera / Q000166:cytology* / Q000235:genetics*; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid; D019699:Thrombospondins / Q000737:chemistry / Q000494:pharmacology; D013997:Time Factors
chemical_list: D018955:CD36 Antigens; D037161:Galectins; D008024:Ligands; D009285:Naphthoquinones; D011993:Recombinant Fusion Proteins; D019699:Thrombospondins; C052704:2-methylthio-1,4-naphthoquinone; D005982:Glutathione Transferase