Glutamate-mediated signaling in Schistosoma mansoni: A novel glutamate receptor is expressed in neurons and the female reproductive tract

Taman, Amira; Ribeiro, Paula

doi:10.1016/j.molbiopara.2010.12.001

Cited by 35 publications

(29 citation statements)

References 42 publications

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“…Venom allergen-like proteins (VALs) of platyhelminths are members of the SCP/TAPS (Sperm-Coating Protein/Tpx-1/Ag5/PR-1/Sc7) protein superfamily and hypothesized to play not only roles in spermatogenesis but also beyond [69], which led to the choice of VAL7 (Smp_070240). The metabotropic glutamate receptor (Smp_128940; [70]) was selected as a representative for cell surface receptors and its potential role in the nervous system of adult male and female schistosomes [71]. Finally, GCP was included due to its hypothesized role in male-female interaction [72].…”

Section: Resultsmentioning

confidence: 99%

Imatinib Treatment Causes Substantial Transcriptional Changes in Adult Schistosoma mansoni In Vitro Exhibiting Pleiotropic Effects

et al. 2014

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BackgroundSchistosome parasites cause schistosomiasis, one of the most important infectious diseases worldwide. For decades Praziquantel (PZQ) is the only drug widely used for controlling schistosomiasis. The absence of a vaccine and fear of PZQ resistance have motivated the search for alternatives. Studies on protein kinases (PKs) demonstrated their importance for diverse physiological processes in schistosomes. Among others two Abl tyrosine kinases, SmAbl1 and SmAbl2, were identified in Schistosoma mansoni and shown to be transcribed in the gonads and the gastrodermis. SmAbl1 activity was blocked by Imatinib, a known Abl-TK inhibitor used in human cancer therapy (Gleevec/Glivec). Imatinib exhibited dramatic effects on the morphology and physiology of adult schistosomes in vitro causing the death of the parasites.Methodology/Principal FindingsHere we show modeling data supporting the targeting of SmAbl1/2 by Imatinib. A biochemical assay confirmed that SmAbl2 activity is also inhibited by Imatinib. Microarray analyses and qRT-PCR experiments were done to unravel transcriptional processes influenced by Imatinib in adult schistosomes in vitro demonstrating a wide influence on worm physiology. Surface-, muscle-, gut and gonad-associated processes were affected as evidenced by the differential transcription of e.g. the gynecophoral canal protein gene GCP, paramyosin, titin, hemoglobinase, and cathepsins. Furthermore, transcript levels of VAL-7 and egg formation-associated genes such as tyrosinase 1, p14, and fs800-like were affected as well as those of signaling genes including a ribosomal protein S6 kinase and a glutamate receptor. Finally, a comparative in silico analysis of the obtained microarray data sets and previous data analyzing the effect of a TGFβR1 inhibitor on transcription provided first evidence for an association of TGFβ and Abl kinase signaling. Among others GCP and egg formation-associated genes were identified as common targets.Conclusions/SignificanceThe data affirm broad negative effects of Imatinib on worm physiology substantiating the role of PKs as interesting targets.

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Section: Resultsmentioning

confidence: 99%

Imatinib Treatment Causes Substantial Transcriptional Changes in Adult Schistosoma mansoni In Vitro Exhibiting Pleiotropic Effects

et al. 2014

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“…In addition, SmGBP shares sequence homology with other glutamate receptors of S. mansoni , including the previously described SmGluR [25], as well as predicted mGluRs of flatworm species for which genome sequences are available, notably Schistosoma japonicum and the planarian Schmidtea mediterranea . A search of the S. japonicum database available at GeneDB (http://www.genedb.org/) found a protein sequence (Sjp 0088520) of 485 amino acid residues that is almost identical to SmGBP (92% homology) and another highly homologous 486 amino acid sequence was detected in the S. mediterranea genome database (v31.015264) (http://smedgd.neuro.utah.edu) [26].…”

Section: Resultsmentioning

confidence: 81%

“…We have previously reported that one of these sequences, named SmGluR, encodes a functional glutamate receptor, which is expressed in part in the worm's central nervous system [25]. In this study we describe the second and most unusual of these predicted receptors.…”

Section: Introductionmentioning

confidence: 89%

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Characterization of a Truncated Metabotropic Glutamate Receptor in a Primitive Metazoan, the Parasitic Flatworm Schistosoma mansoni

Taman

Ribeiro

2011

PLoS ONE

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A novel glutamate-binding protein was identified in Schistosoma mansoni. The protein (SmGBP) is related to metabotropic glutamate receptors from other species and has a predicted glutamate binding site located within a Venus Flytrap module but it lacks the heptahelical transmembrane segment that normally characterizes these receptors. The SmGBP cDNA was cloned, verified by 5′ and 3′ Rapid Amplification of cDNA Ends (RACE) and shown to be polyadenylated at the 3′end, suggesting the transcript is full-length. The cloned cDNA was subsequently expressed in bacteria and shown to encode a functional glutamate-binding protein. Other studies, using a specific peptide antibody, determined that SmGBP exists in two forms, a monomer of the expected size and a stable but non-covalent dimer. The monomer and dimer are both present in the membrane fraction of S. mansoni and are resistant to extraction with high-salt, alkaline pH and urea, suggesting SmGBP is either an integral membrane protein or a peripheral protein that is tightly associated with the membrane. Surface biotinylation experiments combined with western blot analyses and confocal immunolocalization revealed that SmGBP localized to the surface membranes of adult male schistosomes, especially the dorsal tubercles. In contrast, we detected little or no expression of SmGBP either in the females or larval stages. A comparative quantitative PCR analysis confirmed that the level of SmGBP expression is several-fold higher in male worms than cercariae, and it is barely detectable in adult females. Together, the results identify SmGBP as a new type of schistosome glutamate receptor that is both gender- and stage-specific. The high-level expression of this protein in the male tubercles suggests a possible role in host-parasite interaction.

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“…The tegument of S. mansoni is an important structure involved in the absorption of nutrients, secretion of some products, variety of movements, including rapid shortening and extension of the body, typical wavy and peristaltic movement along the body axis (anterior and posterior) 39 . Therefore, the worm’s tegument is the critical target for imidazolidine derivatives as has been shown in other studies 16 - 19 .…”

Section: Discussionmentioning

confidence: 87%

Synthesis and biological evaluation of novel imidazolidine derivatives as candidates to schistosomicidal agents

Rocha

Lima

Silva

et al. 2017

Rev. Inst. Med. trop. S. Paulo

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Introduction: Schistosomiasis is an infectious parasitic disease caused by trematodes of the genus Schistosoma, which threatens at least 258 million people worldwide and its control is dependent on a single drug, praziquantel. The aim of this study was to evaluate the anti-Schistosoma mansoni activity in vitro of novel imidazolidine derivatives. Material and methods: We synthesized two novel imidazolidine derivatives: (LPSF/PTS10) (Z)-1-(2-chloro-6-fluorobenzyl)-4-(4-dimethylaminobenzylidene)-5-thioxoimidazolidin-2-one and (LPSF/PTS23) (Z)-1-(2-chloro-6-fluoro-benzyl)-5-thioxo-4-(2,4,6-trimethoxy-benzylidene)-imidazolidin-2-one. The structures of two compounds were determined by spectroscopic methods. During the biological assays, parameters such as motility, oviposition, mortality and analysis by Scanning Electron Microscopy were performed.Results: LPSF/PTS10 and LPSF/PTS23 were considered to be active in the separation of coupled pairs, mortality and to decrease the motor activity. In addition, LPSF/PTS23 induced ultrastructural alterations in worms, after 24 h of contact, causing extensive erosion over the entire body of the worms.Conclusion: The imidazolidine derivatives containing the trimetoxy and benzylidene halogens showed promising in vitro schistosomicidal activity.

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Glutamate-mediated signaling in Schistosoma mansoni: A novel glutamate receptor is expressed in neurons and the female reproductive tract

Cited by 35 publications

References 42 publications

Imatinib Treatment Causes Substantial Transcriptional Changes in Adult Schistosoma mansoni In Vitro Exhibiting Pleiotropic Effects

Imatinib Treatment Causes Substantial Transcriptional Changes in Adult Schistosoma mansoni In Vitro Exhibiting Pleiotropic Effects

Characterization of a Truncated Metabotropic Glutamate Receptor in a Primitive Metazoan, the Parasitic Flatworm Schistosoma mansoni

Synthesis and biological evaluation of novel imidazolidine derivatives as candidates to schistosomicidal agents

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