title: Tollip, a negative regulator of TLR-signalling, is encoded by twin genes in salmonid fish.
abstract: The factor Tollip is known to dampen TLR2- and TLR4-mediated signalling in mammals. No negative regulator of the piscine TLR-signalling cascade has been described so far, albeit a sizable collection of factors contributing to this ancient pathogen-sensing system are known from fish to date. We identified two closely related Tollip-encoding genes in Atlantic salmon (Salmo salar) and the respective ortholog mRNA molecules in rainbow trout (Oncorhynchus mykiss). The salmonid Tollip genes are segmented into 6 exons, similar to the human orthologous gene. The protein-encoding sequences are homologous to >97% among the twin factors and also between the species. Both encoded proteins contain a C2 domain and an ubiquitin system component, which are also characteristic features of the mammalian Tollip factor. We analysed the expression of these genes in trout. Both Tollip-encoding genes are ubiquitously and also equally expressed, as indicated by similar mRNA concentrations of both factors in any one tissue. Tollip expression was found to be up-regulated by viral infection. Our data suggest that the Tollip genes were duplicated before salmon and trout were evolutionary separated. Moreover, pathways dampening the activity of the TLR-cascade may have been conserved from lower vertebrates to mammals since Tollip, as a respective key factor has been highly conserved from fish to human.
authors.affiliation: Research Institute for the Biology of Farm Animals (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Rebl
authors.forename: Bjørn
authors.initials: B
authors.lastname: Høyheim
authors.forename: Uwe
authors.initials: U
authors.lastname: Fischer
authors.forename: Bernd
authors.initials: B
authors.lastname: Köllner
authors.forename: Edda
authors.initials: E
authors.lastname: Siegl
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Seyfert
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005393:Fish Diseases / Q000276:immunology / Q000821:virology; D020869:Gene Expression Profiling; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D029141:Novirhabdovirus; D017686:Oncorhynchus mykiss / Q000235:genetics*; D010802:Phylogeny; D012333:RNA, Messenger / Q000378:metabolism; D018353:Rhabdoviridae Infections / Q000276:immunology / Q000662:veterinary; D020317:Salmo salar / Q000235:genetics*; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D051193:Toll-Like Receptors