Abstract
BackgroundSchistosomes 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 FindingsWe 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.ConclusionsAdult 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.
Highlights
Schistosomes are parasitic blood flukes infecting approximately 200 million people globally [1] of which 20 million have severe disease; 250,000 deaths are directly or indirectly attributable each year to schistosomiasis [2]
Adult worms of S. japonicum possess insulin receptors that can 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
Summary
Schistosomes are parasitic blood flukes infecting approximately 200 million people globally [1] of which 20 million have severe disease; 250,000 deaths are directly or indirectly attributable each year to schistosomiasis [2]. The tegument, the outermost surface of the intra-mammalian stages of schistosomes, is a dynamic host-interactive layer involved in nutrition, immune evasion, excretion and signal transduction. As sensing and responding to environmental factors are essential in the complex life cycle of schistosomes, studying on signal transduction molecules and their functional mechanisms will be necessary for elucidating schistosome host-parasite interactions and parasite biology [6,7,8]. Receptor tyrosine kinases (RTKs) are high affinity cell surface receptors that bind many ligands including hormones, growth factors, cytokines, and trigger different signalling cellular cascades for the control and regulation of cell proliferation and differentiation [11]. 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
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call