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: e9868-1-e9868-13. doi:10.1371/journal.pone.0009868


Author You, Hong
Zhang, Wenbao
Jones, Malcolm K.
Gobert, Geoffrey N.
Mulvenna, Jason
Rees, Glynn
Spanevello, Mark
Blair, David
Duke, Mary
Brehm, Klaus
McManus, Donald P.
Title Cloning and characterisation of Schistosoma japonicum insulin receptors
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2010-03
Sub-type Article (original research)
DOI 10.1371/journal.pone.0009868
Open Access Status DOI
Volume 5
Issue 3
Start page e9868-1
End page e9868-13
Total pages 13
Editor Damian Pattinson
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2011
Language eng
Formatted 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.

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.


Keyword Growth factor receptor
Protein-tyrosine kinases
Host-parasite interplay
Differential regulation
Ligand specificity
Signaling pathways
Crystal structure
Gene expression
Glucose uptake
Blood flukes
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 35 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 39 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 11 Apr 2010, 00:01:26 EST