title: Molecular characterization of host-parasite cell signalling in Schistosoma mansoni during early development.
abstract: During infection of their human definitive host, schistosomes transform rapidly from free-swimming infective cercariae in freshwater to endoparasitic schistosomules. The 'somules' next migrate within the skin to access the vasculature and are surrounded by host molecules that might activate intracellular pathways that influence somule survival, development and/or behaviour. However, such 'transactivation' by host factors in schistosomes is not well defined. In the present study, we have characterized and functionally localized the dynamics of protein kinase C (PKC) and extracellular signal-regulated kinase (ERK) activation during early somule development in vitro and demonstrate activation of these protein kinases by human epidermal growth factor, insulin, and insulin-like growth factor I, particularly at the parasite surface. Further, we provide evidence that support the existence of specialized signalling domains called lipid rafts in schistosomes and propose that correct signalling to ERK requires proper raft organization. Finally, we show that modulation of PKC and ERK activities in somules affects motility and reduces somule survival. Thus, PKC and ERK are important mediators of host-ligand regulated transactivation events in schistosomes, and represent potential targets for anti-schistosome therapy aimed at reducing parasite survival in the human host.
authors.affiliation: Molecular Parasitology Laboratory, School of Life Sciences, Pharmacy and Chemistry, Kingston University, KT1 2EE, United Kingdom.
authors.forename: Margarida
authors.initials: M
authors.lastname: Ressurreição
authors.affiliation: Molecular Parasitology Laboratory, School of Life Sciences, Pharmacy and Chemistry, Kingston University, KT1 2EE, United Kingdom.
authors.forename: Firat
authors.initials: F
authors.lastname: Elbeyioglu
authors.affiliation: Molecular Parasitology Laboratory, School of Life Sciences, Pharmacy and Chemistry, Kingston University, KT1 2EE, United Kingdom.
authors.forename: Ruth S
authors.initials: RS
authors.lastname: Kirk
authors.affiliation: Department of Life Sciences, The Natural History Museum, London, SW7 5BD, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Rollinson
authors.affiliation: Department of Life Sciences, The Natural History Museum, London, SW7 5BD, United Kingdom.
authors.forename: Aidan M
authors.initials: AM
authors.lastname: Emery
authors.affiliation: Molecular Parasitology Laboratory, School of Life Sciences, Pharmacy and Chemistry, Kingston University, KT1 2EE, United Kingdom.
authors.forename: Nigel M
authors.initials: NM
authors.lastname: Page
authors.affiliation: Molecular Parasitology Laboratory, School of Life Sciences, Pharmacy and Chemistry, Kingston University, KT1 2EE, United Kingdom.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Walker
mesh_terms: D000818:Animals; D004815:Epidermal Growth Factor / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008124:Locomotion; D021962:Membrane Microdomains / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D012550:Schistosoma mansoni / Q000254:growth & development*; D015398:Signal Transduction; D016019:Survival Analysis
chemical_list: D007328:Insulin; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases