Cloning and Characterisation of Schistosoma japonicum Insulin Receptors

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.

A retinoid X receptor (RXR1) homolog from Schistosoma japonicum: Its ligand-binding domain may bind to 9-cis-retinoic acid

“…For Western blotting, 21 d worm antigen was prepared from S. japonicum worms as described [18]. The 21 d worm extracts and purified recombinant His/SjRXR1 (LBD) fusion protein were separated by SDS/PAGE (12% gel) and transferred to a nitrocellulose membrane (Whatman, Germany).…”

Neuroimmunoendocrine Interactions in Murine Cysticercosis: From the Lab Bench Work to Its Possible Applications in Controlling Porcine Cysticercosis and Human Neurocysticercosis

“…Schistosoma mansonii Echinococcus multilocularis (Ramachandran et al, 1996) Insulin Receptor Schistosoma mansonii Schistosoma japonicum Echinococcus multilocularis (Khayath et al, 2007) (You et al, 2010) (Konrad et al, 2003) Retinoid X receptor Schistosomamansonii Brugia malayi (Freebern et al, 1999 (Sani et al, 1985) Estrogen Receptor…”

The cell biology of schistosomes: a window on the evolution of the early metazoa

“…The characterisation of two protein tyrosine kinase insulin-type receptors, first in S. mansoni (SmIR-1, SmIR-2; (Khayath et al 2007)) and then in S. japonicum (You et al 2010), together with identification of signalling pathway components in the respective genomes , has underlined the ancient origins of this pathway. In consequence, it has been strongly implied that schistosomes utilise host insulin to regulate of their glucose metabolism .…”