title: Evidence for Integrin - Venus Kinase Receptor 1 Alliance in the Ovary of Schistosoma mansoni Females Controlling Cell Survival.
abstract: In metazoan integrin signaling is an important process of mediating extracellular and intracellular communication processes. This can be achieved by cooperation of integrins with growth factor receptors (GFRs). Schistosoma mansoni is a helminth parasite inducing schistosomiasis, an infectious disease of worldwide significance for humans and animals. First studies on schistosome integrins revealed their role in reproductive processes, being involved in spermatogenesis and oogenesis. With respect to the roles of eggs for maintaining the parasite´s life cycle and for inducing the pathology of schistosomiasis, elucidating reproductive processes is of high importance. Here we studied the interaction of the integrin receptor Smβ-Int1 with the venus kinase receptor SmVKR1 in S. mansoni. To this end we cloned and characterized SmILK, SmPINCH, and SmNck2, three putative bridging molecules for their role in mediating Smβ-Int1/SmVKR1 cooperation. Phylogenetic analyses showed that these molecules form clusters that are specific for parasitic platyhelminths as it was shown for integrins before. Transcripts of all genes colocalized in the ovary. In Xenopus oocytes germinal vesicle breakdown (GVBD) was only induced if all members were simultaneously expressed. Coimmunoprecipitation results suggest that a Smβ-Int1-SmILK-SmPINCH-SmNck2-SmVKR1 complex can be formed leading to the phosphorylation and activation of SmVKR1. These results indicate that SmVKR1 can be activated in a ligand-independent manner by receptor-complex interaction. RNAi and inhibitor studies to knock-down SmILK as a representative complex member concurrently revealed effects on the extracellular matrix surrounding the ovary and oocyte localization within the ovary, oocyte survival, and egg production. By TUNEL assays, confocal laser scanning microscopy (CLSM), Caspase-3 assay, and transcript profiling of the pro-apoptotic BCL-2 family members BAK/BAX we obtained first evidence for roles of this signaling complex in mediating cell death in immature and primary oocytes. These results suggest that the Smβ-Int1/SmVKR1 signaling complex is important for differentiation and survival in oocytes of paired schistosomes.
authors.affiliation: Institute for Parasitology, Justus-Liebig-University, Giessen, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Gelmedin
authors.affiliation: CIIL - Center for Infection and Immunity of Lille Inserm U1019 - CNRS UMR 8204, University Lille, Lille, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Morel
authors.affiliation: Institute for Parasitology, Justus-Liebig-University, Giessen, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Hahnel
authors.affiliation: UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, CNRS UMR 8576, University Lille, Lille, France.
authors.forename: Katia
authors.initials: K
authors.lastname: Cailliau
authors.affiliation: CIIL - Center for Infection and Immunity of Lille Inserm U1019 - CNRS UMR 8204, University Lille, Lille, France.
authors.forename: Colette
authors.initials: C
authors.lastname: Dissous
authors.affiliation: Institute for Parasitology, Justus-Liebig-University, Giessen, Germany.
authors.forename: Christoph G
authors.initials: CG
authors.lastname: Grevelding
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D006224:Cricetinae; D004195:Disease Models, Animal; D005260:Female; D055785:Gene Knockdown Techniques; D015801:Helminth Proteins / Q000378:metabolism*; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D016023:Integrins / Q000378:metabolism*; D008647:Mesocricetus; D008856:Microscopy, Fluorescence; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D010053:Ovary / Q000166:cytology / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012550:Schistosoma mansoni / Q000472:pathogenicity*; D012555:Schistosomiasis mansoni / Q000378:metabolism* / Q000382:microbiology; D014982:Xenopus laevis
chemical_list: D015801:Helminth Proteins; D016023:Integrins; D011505:Protein-Tyrosine Kinases