Cloning and characterisation of Schistosoma japonicum insulin receptors
You, Hong, Zhang, Wenbao, Jones, Malcolm K., Gobert, Geoffrey N. , Mulvenna, Jason, Rees, Glynn, Spanevello, Mark, Blair, David, Duke, Mary, Brehm, Klaus, and McManus, Donald P. (2010) Cloning and characterisation of Schistosoma japonicum insulin receptors. PLoS ONE, 5 (3). pp. 1-13.
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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.
|Item Type:||Article (Refereed Research - C1)|
Copyright: © 2010 You et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
|Date Deposited:||10 May 2011 11:21|
|FoR Codes:||06 BIOLOGICAL SCIENCES > 0603 Evolutionary Biology > 060307 Host-Parasite Interactions @ 50%
06 BIOLOGICAL SCIENCES > 0604 Genetics > 060409 Molecular Evolution @ 50%
|SEO Codes:||92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 50%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920120 Zoonoses @ 50%
|Citation Count from Web of Science||