Cloning and characterisation of Schistosoma japonicum insulin receptors.

<h4>Background</h4>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 biolog...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2c9aed8618f849e7bbaac9be43059ee0
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spelling	oai:doaj.org-article:2c9aed8618f849e7bbaac9be43059ee02021-12-02T20:11:54ZCloning and characterisation of Schistosoma japonicum insulin receptors.1932-620310.1371/journal.pone.0009868https://doaj.org/article/2c9aed8618f849e7bbaac9be43059ee02010-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20352052/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions</h4>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.Hong YouWenbao ZhangMalcolm K JonesGeoffrey N GobertJason MulvennaGlynn ReesMark SpanevelloDavid BlairMary DukeKlaus BrehmDonald P McManusPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 3, p e9868 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 Cloning and characterisation of Schistosoma japonicum insulin receptors.
description	<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions</h4>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.
format	article
author	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
author_facet	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
author_sort	Hong You
title	Cloning and characterisation of Schistosoma japonicum insulin receptors.
title_short	Cloning and characterisation of Schistosoma japonicum insulin receptors.
title_full	Cloning and characterisation of Schistosoma japonicum insulin receptors.
title_fullStr	Cloning and characterisation of Schistosoma japonicum insulin receptors.
title_full_unstemmed	Cloning and characterisation of Schistosoma japonicum insulin receptors.
title_sort	cloning and characterisation of schistosoma japonicum insulin receptors.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/2c9aed8618f849e7bbaac9be43059ee0
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Cloning and characterisation of Schistosoma japonicum insulin receptors.

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