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A bone morphogenetic protein homologue in the parasitic flatworm, Schistosoma mansoni.

ABSTRACT: Members of the bone morphogenetic protein (BMP) subfamily of cytokines control many aspects of metazoan development including patterning and organogenesis. Despite the recognition that schistosomes possess key components of a BMP signaling pathway, a BMP-like ligand in the parasitic flatworm Schistosoma mansoni remained elusive. Here, we describe the cloning and characterisation of an S. mansoni BMP (SmBMP). SmBMP is most closely related to BMP homologues from the free-living flatworms Schmidtea mediterranea and Dugesia japonica, with 51% and 47% identity at the amino acid level, respectively. Based on reverse transcription-PCR, SmBMP is expressed throughout the mammalian life-cycle of the parasite in both male and female schistosomes. In support of these results, antibodies to SmBMP successfully immunoprecipitated the protein in adult male and female antigen preparations with more protein detected in male parasites. Immunofluorescent studies localised SmBMP to the protonephridia of adult parasites, and SmBMP was identified in the excretory/secretory products of adult male parasites via immunoprecipitation. With the previous description of a TGF-beta subfamily homologue in S. mansoni, ligands representing both arms of the TGF-beta superfamily have now been described in this trematode.

SUBMITTER: Freitas TC

PROVIDER: S-EPMC2852128 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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A bone morphogenetic protein homologue in the parasitic flatworm, Schistosoma mansoni.

Freitas Tori C TC Jung Euihye E Pearce Edward J EJ

International journal for parasitology 20080815 3

Members of the bone morphogenetic protein (BMP) subfamily of cytokines control many aspects of metazoan development including patterning and organogenesis. Despite the recognition that schistosomes possess key components of a BMP signaling pathway, a BMP-like ligand in the parasitic flatworm Schistosoma mansoni remained elusive. Here, we describe the cloning and characterisation of an S. mansoni BMP (SmBMP). SmBMP is most closely related to BMP homologues from the free-living flatworms Schmidtea ...[more]

PMID: 18765241

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Project description:Over 200 million people have, and another 600 million are at risk of contracting, schistosomiasis, one of the major neglected tropical diseases. Transmission of this infection, which is caused by helminth parasites of the genus Schistosoma, depends upon the release of parasite eggs from the human host. However, approximately 50% of eggs produced by schistosomes fail to reach the external environment, but instead become trapped in host tissues where pathological changes caused by the immune responses to secreted egg antigens precipitate disease. Despite the central importance of egg production in transmission and disease, relatively little is understood of the molecular processes underlying the development of this key life stage in schistosomes. Here, we describe a novel parasite-encoded TGF-beta superfamily member, Schistosoma mansoni Inhibin/Activin (SmInAct), which is key to this process. In situ hybridization localizes SmInAct expression to the reproductive tissues of the adult female, and real-time RT-PCR analyses indicate that SmInAct is abundantly expressed in ovipositing females and the eggs they produce. Based on real-time RT-PCR analyses, SmInAct transcription continues, albeit at a reduced level, both in adult worms isolated from single-sex infections, where reproduction is absent, and in parasites from IL-7R(-/-) mice, in which viable egg production is severely compromised. Nevertheless, Western analyses demonstrate that SmInAct protein is undetectable in parasites from single-sex infections and from infections of IL-7R(-/-) mice, suggesting that SmInAct expression is tightly linked to the reproductive potential of the worms. A crucial role for SmInAct in successful embryogenesis is indicated by the finding that RNA interference-mediated knockdown of SmInAct expression in eggs aborts their development. Our results demonstrate that TGF-beta signaling plays a major role in the embryogenesis of a metazoan parasite, and have implications for the development of new strategies for the treatment and prevention of an important and neglected human disease.

Project description:Schistosomiasis is endemic in over 70 countries, in which more than 200 million people are infected with the various schistosome species. Understanding the physiological processes underlying key developmental events could be useful in developing novel chemotherapeutic reagents or infection intervention strategies. Calmodulin is a small, calcium-sensing protein found in all eukaryotes and, although the protein has been previously identified in various Schistosoma mansoni stages and implicated in egg hatching and miracidia transformation, few molecular and functional data are available for this essential protein. Herein, we report the molecular cloning, expression, and functional characterization of calmodulin in the miracidia and primary sporocyst stages of S. mansoni. Two transcripts, SmCaM1 and SmCaM2, were cloned and sequenced, and a recombinant SmCaM1 protein was expressed in Escherichia coli and used to generate anti-CaM antibodies. The 2 protein sequences were highly conserved when compared to other model organisms. The alignment of the predicted proteins of both SmCaM1 and SmCaM2 exhibited 99% identity to each other and 97-98% identity with mammalian calmodulins. Analysis of steady-state transcript abundance indicate that the 2 calmodulin transcripts differ in their stage-associated expression patterns, although the CaM protein isotype appears to be constitutively expressed during early larval development. Application of RNAi to larval parasites results in a "stunted growth" phenotype in sporocysts with 30 and 35% reduction in transcript abundance for SmCaM1 and SmCaM2, respectively, and a corresponding 35% reduction in protein level after incubation in double-stranded RNA. Differential expression of CaM transcripts during early larval development and a growth defect-inducing effect associated with partial transcript and protein inhibition as a result of RNAi suggest a potentially important role of calmodulin during early larval development.

Project description:BackgroundHeat shock proteins (HSPs) are evolutionarily conserved proteins, produced by cells in response to hostile environmental conditions, that are vital to organism homeostasis. Here, we undertook the first detailed molecular bioinformatic analysis of these important proteins and mapped their tissue expression in the human parasitic blood fluke, Schistosoma mansoni, one of the causative agents of the neglected tropical disease human schistosomiasis.MethodsUsing bioinformatic tools we classified and phylogenetically analysed HSP family members in schistosomes, and performed transcriptomic, phosphoproteomic, and interactomic analysis of the S. mansoni HSPs. In addition, S. mansoni HSP protein expression was mapped in intact parasites using immunofluorescence.ResultsFifty-five HSPs were identified in S. mansoni across five HSP families; high conservation of HSP sequences were apparent across S. mansoni, Schistosoma haematobium and Schistosoma japonicum, with S. haematobium HSPs showing greater similarity to S. mansoni than those of S. japonicum. For S. mansoni, differential HSP gene expression was evident across the various parasite life stages, supporting varying roles for the HSPs in the different stages, and suggesting that they might confer some degree of protection during life stage transitions. Protein expression patterns of HSPs were visualised in intact S. mansoni cercariae, 3 h and 24 h somules, and adult male and female worms, revealing HSPs in the tegument, cephalic ganglia, tubercles, testes, ovaries as well as other important organs. Analysis of putative HSP protein-protein associations highlighted proteins that are involved in transcription, modification, stability, and ubiquitination; functional enrichment analysis revealed functions for HSP networks in S. mansoni including protein export for HSP 40/70, and FOXO/mTOR signalling for HSP90 networks. Finally, a total of 76 phosphorylation sites were discovered within 17 of the 55 HSPs, with 30 phosphorylation sites being conserved with those of human HSPs, highlighting their likely core functional significance.ConclusionsThis analysis highlights the fascinating biology of S. mansoni HSPs and their likely importance to schistosome function, offering a valuable and novel framework for future physiological investigations into the roles of HSPs in schistosomes, particularly in the context of survival in the host and with the aim of developing novel anti-schistosome therapeutics.

Dataset Information

A bone morphogenetic protein homologue in the parasitic flatworm, Schistosoma mansoni.

Publications

A bone morphogenetic protein homologue in the parasitic flatworm, Schistosoma mansoni.

Similar Datasets

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