Titre :

Transcriptome Analyses of Inhibitor-treated Schistosome Females Provide Evidence for Cooperating Src-kinase and TGFβ Receptor Pathways Controlling Mitosis and Eggshell Formation

Auteur(s) :

Buro, Christin [Auteur]
Justus-Liebig-Universität Gießen = Justus Liebig University [JLU]
Oliveira, Katia C. [Auteur]
Universidade de São Paulo = University of São Paulo [USP]
Lu, Zhigang [Auteur]
Justus-Liebig-Universität Gießen = Justus Liebig University [JLU]
Leutner, Silke [Auteur]
Justus-Liebig-Universität Gießen = Justus Liebig University [JLU]
Beckmann, Svenja [Auteur]
Justus-Liebig-Universität Gießen = Justus Liebig University [JLU]
Dissous, Colette [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Cailliau, Katia [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Verjovski-Almeida, Sergio [Auteur]
Universidade de São Paulo = University of São Paulo [USP]
Grevelding, Christoph G. [Auteur]
Justus-Liebig-Universität Gießen = Justus Liebig University [JLU]

Titre de la revue :

PLoS Pathogens

Numéro :

9

Pagination :

e1003448

Date de publication :

2013-06-13

ISSN :

1553-7374

Mot(s)-clé(s) en anglais :

microarrays
eggs
DNA transcription
herbs
schistosoma
ovaries
schistosoma mansoni
xenopus oocytes

Discipline(s) HAL :

Chimie/Chimie théorique et/ou physique

Résumé en anglais : [en]

Schistosome parasites cause schistosomiasis, one of the most prevalent parasitemias worldwide affecting humans and animals. Constant pairing of schistosomes is essential for female sexual maturation and egg production, ...
Lire la suite >Schistosome parasites cause schistosomiasis, one of the most prevalent parasitemias worldwide affecting humans and animals. Constant pairing of schistosomes is essential for female sexual maturation and egg production, which causes pathogenesis. Female maturation involves signaling pathways controlling mitosis and differentiation within the gonads. In vitro studies had shown before that a Src-specific inhibitor, Herbimycin A (Herb A), and a TGFβ receptor (TβR) inhibitor (TRIKI) have physiological effects such as suppressed mitoses and egg production in paired females. As one Herb A target, the gonad-specifically expressed Src kinase SmTK3 was identified. Here, we comparatively analyzed the transcriptome profiles of Herb A- and TRIKI-treated females identifying transcriptional targets of Src-kinase and TβRI pathways. After demonstrating that TRIKI inhibits the schistosome TGFβreceptor SmTβRI by kinase assays in Xenopus oocytes, couples were treated with Herb A, TRIKI, or both inhibitors simultaneously in vitro. RNA was isolated from females for microarray hybridizations and transcription analyses. The obtained data were evaluated by Gene Ontology (GO) and Ingenuity Pathway Analysis (IPA), but also by manual classification and intersection analyses. Finally, extensive qPCR experiments were done to verify differential transcription of candidate genes under inhibitor influence but also to functionally reinforce specific physiological effects. A number of genes found to be differentially regulated are associated with mitosis and differentiation. Among these were calcium-associated genes and eggshell-forming genes. In situ hybridization confirmed transcription of genes coding for the calcium sensor hippocalcin, the calcium transporter ORAI-1, and the calcium-binding protein calmodulin-4 in the reproductive system pointing to a role of calcium in parasite reproduction. Functional qPCR results confirmed an inhibitor-influenced, varying dependence of the transcriptional activities of Smp14, Smp48, fs800, a predicted eggshell precursor protein and SmTYR1. The results show that eggshell-formation is regulated by at least two pathways cooperatively operating in a balanced manner to control egg production.Lire moins >

Langue :

Anglais

Audience :

Non spécifiée

Établissement(s) :

CNRS
Université de Lille

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017
• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Équipe(s) de recherche :

Régulation des signaux de division

Date de dépôt :

2020-02-12T15:44:33Z
2021-04-21T09:48:45Z