| Cloning and characterisation of Schistosoma japonicum insulin receptors. | |
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MedLine Citation:
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PMID: 20352052 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. METHODOLOGY/PRINCIPAL FINDINGS: 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. |
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Authors:
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Hong You; Wenbao Zhang; Malcolm K Jones; Geoffrey N Gobert; Jason Mulvenna; Glynn Rees; Mark Spanevello; David Blair; Mary Duke; Klaus Brehm; Donald P McManus |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-03-24 |
Journal Detail:
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Title: PloS one Volume: 5 ISSN: 1932-6203 ISO Abbreviation: PLoS ONE Publication Date: 2010 |
Date Detail:
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Created Date: 2010-03-30 Completed Date: 2011-01-11 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101285081 Medline TA: PLoS One Country: United States |
Other Details:
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Languages: eng Pagination: e9868 Citation Subset: IM |
Affiliation:
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Queensland Institute of Medical Research, Brisbane, Queensland, Australia. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cloning, Molecular Crystallography, X-Ray / methods Gene Expression Regulation* Glucose / metabolism Humans Insulin / metabolism Ligands Phylogeny Protein Structure, Tertiary Receptor, Insulin / genetics*, metabolism Schistosoma japonicum / genetics*, metabolism* Schistosomiasis / parasitology Two-Hybrid System Techniques |
| Grant Support | |
ID/Acronym/Agency:
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ID071657MA//Wellcome Trust |
| Chemical | |
Reg. No./Substance:
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0/Ligands; 11061-68-0/Insulin; 50-99-7/Glucose; EC 2.7.10.1/Receptor, Insulin |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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