Growth factor receptors in helminth parasites: Signalling and host–parasite relationships

Dissous, Colette; Khayath, N.; Vicogne, Jérôme; Capron, Moníque

doi:10.1016/j.febslet.2006.03.046

Cited by 57 publications

(49 citation statements)

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“…D ifferent studies have demonstrated that the development of S. mansoni could be dependent on host hormones (De Mendonca et al, 2000) and growth factors (Dissous et al, 2006) but the possibility that insulin-dependent mechanisms also occur in schistosomes has been extensively debated. Indeed, the first studies showing that insulin could increase oxygen and glucose uptake, life span and resistance to antibodies of schistosomula (Levi-Schaffer & Smolarsky, 1981) have been further disapproved by other authors who concluded to an insulin independence of schistosomes (Clemens & Basch, 1989).…”

Section: Resultsmentioning

confidence: 99%

Insulin receptors and glucose uptake in the human parasiteSchistosoma mansoni

et al. 2008

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Summary :Very little is known about insulin signalling in schistosomes despite its potential importance in host-parasite molecular dialogue and parasite growth and development. The recent characterization of two insulin receptors (SmIR-1 and SmIR-2) in Schistosoma mansoni has led us to reconsider the question of the potential importance of insulin in host-schistosome interactions. In this work, we demonstrated that insulin could regulate glucose uptake in schistosomes and we investigated the implication of SmIR-1 and SmIR-2 in this process. The possibility that specific inhibitors of SmIR-1 and SmIR-2 tyrosine kinase activities could be developed to target schistosomes is discussed. Résumé

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Section: Resultsmentioning

confidence: 99%

Insulin receptors and glucose uptake in the human parasiteSchistosoma mansoni

et al. 2008

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“…Convincing studies have demonstrated the importance of protein kinases in schistosome growth and development (Dissous et al 2006, Knobloch et al 2007, Beckmann et al 2010a. The effect of anti-cancer drugs on the reproductive activity of parasites as well as on their survival in in vitro culture (shown recently for the Abl-kinase inhibitor Imatinib by Beckmann and Grevelding 2010) reinforces the hypothesis that parasite protein kinases could represent new targets for antischistosomal strategies, but also that piggy-backing cancer drugs for treatment of schistosomiasis is really worth considering (Dissous and Grevelding 2011).…”

Section: Discussionmentioning

confidence: 99%

Schistosoma mansoni polo-like kinases and their function in control of mitosis and parasite reproduction

Dissous

Grevelding

Long

2011

An. Acad. Bras. Ciênc.

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Polo-like kinases are important regulators of cell cycle progression and mitosis. They constitute a family of conserved serine/threonine kinases which are highly related in their catalytic domains and contain polo boxes involved in protein-protein interactions and subcellular localization. In mammals, five Plks (Plk 1-5) encompass diverse roles in centrosome dynamics, spindle formation, intra S-phase and G2/M checkpoints and DNA damage response. Plk1 is a key positive regulator of mitosis and is overexpressed in various types of cancers. Plk4 is a divergent member of the Plk family, with essential functions in centriole duplication. Homozygous disruption of Plk1 or Plk4 in mice is lethal in embryos. Two Plk members SmPlk1 and SmSak, homologous to Plk1 and Plk4 respectively, are present in the parasitic platyhelminth Schistosoma mansoni. Structural and functional analyses of SmPlk1 have demonstrated its conserved function in the regulation of cell cycle G2/M transition in Xenopus oocytes. The anti-cancer drug BI 2536 (the most potent and selective Plk1 inhibitor) inhibits specifically the catalytic activity of SmPlk1 and induced profound alterations in schistosome gonads, indicating a role of SmPlk1 in parasite gametogenesis and its potential as a novel chemotherapeutic target against schistosomiasis. Functions of SmSak in cell cycle regulation and schistosome gonad development are currently investigated.Key words: cell cycle, Polo-like kinases, reproduction, Schistosoma mansoni. SCHISTOSOME BIOLOGY AND PROTEIN KINASESSchistosomiasis is a water-borne disease and one of the most important parasitic diseases worldwide, with more than 200 million people infected. Transmission of schistosomes is endemic in over 70 tropical and subtropical countries. Control of schistosomiasis relies in priority on mass treatment of human populations with Praziquantel (PZQ), a drug which has been proven for decades to be efficient to reduce morbidity and mortality due to schistosomiasis. However, its widespread use and its inefficacy on juvenile parasites raise fears that schistosomes will develop resistance to PZQ, and there is an urgent need to Correspondence to: Colette Dissous E-mail: colette.dissous@pasteur-lille.fr find alternative drugs and novel concepts to fight schistosomes (Doenhoff et al. 2008).Mating and sexual maturation of adult male and female worms of S. mansoni in the human host lead to the production of numerous eggs which are responsible for transmission, but also for the pathology of schistosomiasis. Eggs are eliminated in faeces, and they assure parasite transmission through the infection of fresh water molluscs as intermediate hosts. Aside, a large proportion of eggs become trapped into human tissues, and granulomas formed around these eggs have serious pathogenic consequences (Ross et al. 2002). In this context, any strategy that aims to reduce worm fecundity and schistosome reproduction represents a valuable concept to combat schistosomiasis.An Acad Bras Cienc (2011) 83 (2) 628 COLETTE DISSOUS, CHRISTO...

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“…Epidermal growth factor receptor (EGFR), a tyrosine kinase receptor, is another example of growth factor receptors that are expressed on the surface of parasites (Ramachandran, et al, 1996) and has been shown to respond to human EGF (Vicogne, et al, 2004). The role of host factors in schistosome development has been reviewed (Davies and McKerrow, 2003, Dissous, et al, 2006, Escobedo, et al, 2005, Knobloch, et al, 2007.…”

Section: Signals From Host Environmentmentioning

confidence: 99%

Schistosoma mansoni: TGF-β signaling pathways

LoVerde

Osman

Hinck

2007

Experimental Parasitology

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Schistosome parasites have co-evolved an intricate relationship with their human and snail hosts as well as a novel interplay between the adult male and female parasites. We review the role of the TGF-β signaling pathway in parasite development, host-parasite interactions and male-female interactions. The data to date supports multiple roles for the TGF-β signaling pathway throughout schistosome development, in particular in the tegument which is at the interface with the host and between the male and female schistosome, development of vitelline cells in female worms whose genes and development are regulated by a stimulus from the male schistosome and embryogenesis of the egg. The human ligand TGF-β1 has been demonstrated to regulate the expression of a schistosome target gene that encodes a gynecophoric canal protein in the schistosome worm itself. Studies on signaling in schistosomes opens a new era for investigation of host-parasite and malefemale interactions. Index DescriptorsHost-parasite interactions; Male-female interactions; Schistosoma mansoni; Smad; TGF-β Schistosome parasites are muticellular eukaryotic organisms with a complex life cycle that involves mammalian and snail hosts. The vertebrate endoparasitic life cycle begins when a schistosome parasite (cercariae) penetrates the skin of a host, it transforms into a schistosomule and begins its life as an endoparasite. To continue its development it must take advantage of signals from the host. Schistosome parasites stay in the skin and after two days enter the circulation and move to the lungs where they remain for further development. About day 8-15, the parasites leave the lungs and move to the portal circulation of the liver where the male and female worms mate. The male worm, through a set of unknown signals, stimulates female gene expression that results in reproductive development and subsequent egg production. The worm pairs move against the flow of blood into their final niche in the mesenteric veins. This stage of the parasite life cycle takes place in a milieu of host signaling molecules. Co-evolution has allowed the schistosome parasite to sense and respond to host mediators. As with all multicellular eucaryotic organisms, development proceeds through the elaboration and response to extracellular signals. In the case of an endoparasite such as the schistosomes, one must consider both external and internal signaling mechanisms in parasite-host and malefemale signaling pathways.

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Growth factor receptors in helminth parasites: Signalling and host–parasite relationships

Cited by 57 publications

References 61 publications

Insulin receptors and glucose uptake in the human parasiteSchistosoma mansoni

Insulin receptors and glucose uptake in the human parasiteSchistosoma mansoni

Schistosoma mansoni polo-like kinases and their function in control of mitosis and parasite reproduction

Schistosoma mansoni: TGF-β signaling pathways

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