title: Cloning and characterisation of Schistosoma japonicum insulin receptors.
abstract: BACKGROUND
  Schistosomes depend for growth and development on host hormonal signals, which may include the insulin signalling pathway. We cloned and assessed the function of two insulin receptors from Schistosoma japonicum in order to shed light on their role in schistosome biology.
  
  
  RESULTS
  We isolated, from S. japonicum, insulin receptors 1 (SjIR-1) and 2 (SjIR-2) sharing close sequence identity to their S. mansoni homologues (SmIR-1 and SmIR-2). SjIR-1 is located on the tegument basal membrane and the internal epithelium of adult worms, whereas SjIR-2 is located in the parenchyma of males and the vitelline tissue of females. Phylogenetic analysis showed that SjIR-2 and SmIR-2 are close to Echinococcus multilocularis insulin receptor (EmIR), suggesting that SjIR-2, SmIR-2 and EmIR share similar roles in growth and development in the three taxa. Structure homology modelling recovered the conserved structure between the SjIRs and Homo sapiens IR (HIR) implying a common predicted binding mechanism in the ligand domain and the same downstream signal transduction processing in the tyrosine kinase domain as in HIR. Two-hybrid analysis was used to confirm that the ligand domains of SjIR-1 and SjIR-2 contain the insulin binding site. Incubation of adult worms in vitro, both with a specific insulin receptor inhibitor and anti-SjIRs antibodies, resulted in a significant decrease in worm glucose levels, suggesting again the same function for SjIRs in regulating glucose uptake as described for mammalian cells.
  
  
  CONCLUSIONS
  Adult worms of S. japonicum possess insulin receptors that can specifically bind to insulin, indicating that the parasite can utilize host insulin for development and growth by sharing the same pathway as mammalian cells in regulating glucose uptake. A complete understanding of the role of SjIRs in the biology of S. japonicum may result in their use as new targets for drug and vaccine development against schistosomiasis.
authors.affiliation: Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
authors.forename: Hong
authors.initials: H
authors.lastname: You
authors.forename: Wenbao
authors.initials: W
authors.lastname: Zhang
authors.forename: Malcolm K
authors.initials: MK
authors.lastname: Jones
authors.forename: Geoffrey N
authors.initials: GN
authors.lastname: Gobert
authors.forename: Jason
authors.initials: J
authors.lastname: Mulvenna
authors.forename: Glynn
authors.initials: G
authors.lastname: Rees
authors.forename: Mark
authors.initials: M
authors.lastname: Spanevello
authors.forename: David
authors.initials: D
authors.lastname: Blair
authors.forename: Mary
authors.initials: M
authors.lastname: Duke
authors.forename: Klaus
authors.initials: K
authors.lastname: Brehm
authors.forename: Donald P
authors.initials: DP
authors.lastname: McManus
mesh_terms: D000818:Animals; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray / Q000379:methods; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008024:Ligands; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D011972:Receptor, Insulin / Q000235:genetics* / Q000378:metabolism; D012549:Schistosoma japonicum / Q000235:genetics* / Q000378:metabolism*; D012552:Schistosomiasis / Q000469:parasitology; D020798:Two-Hybrid System Techniques
chemical_list: D007328:Insulin; D008024:Ligands; D011972:Receptor, Insulin; D005947:Glucose