Dataset Information

Glucose Uptake in the Human Pathogen Schistosoma mansoni Is Regulated Through Akt/Protein Kinase B Signaling.

ABSTRACT: Background:In Schistosoma mansoni, the facilitated glucose transporter SGTP4, which is expressed uniquely in the apical surface tegumental membranes of the parasite, imports glucose from host blood to support its growth, development, and reproduction. However, the molecular mechanisms that underpin glucose uptake in this blood fluke are not understood. Methods:In this study we employed techniques including Western blotting, immunolocalization, confocal laser scanning microscopy, pharmacological assays, and RNA interference to functionally characterize and map activated Akt in S mansoni. Results:We find that Akt, which could be activated by host insulin and l-arginine, was active in the tegument layer of both schistosomules and adult worms. Blockade of Akt attenuated the expression and evolution of SGTP4 at the surface of the host-invading larval parasite life-stage, and suppressed SGTP4 expression at the tegument in adults; concomitant glucose uptake by the parasite was also attenuated in both scenarios. Conclusions:These findings shed light on crucial mechanistic signaling processes that underpin the energetics of glucose uptake in schistosomes, which may open up novel avenues for antischistosome drug development.

SUBMITTER: McKenzie M

PROVIDER: S-EPMC5989616 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Glucose Uptake in the Human Pathogen Schistosoma mansoni Is Regulated Through Akt/Protein Kinase B Signaling.

McKenzie Maxine M Kirk Ruth S RS Walker Anthony J AJ

The Journal of infectious diseases 20180601 1

<h4>Background</h4>In Schistosoma mansoni, the facilitated glucose transporter SGTP4, which is expressed uniquely in the apical surface tegumental membranes of the parasite, imports glucose from host blood to support its growth, development, and reproduction. However, the molecular mechanisms that underpin glucose uptake in this blood fluke are not understood.<h4>Methods</h4>In this study we employed techniques including Western blotting, immunolocalization, confocal laser scanning microscopy, p ...[more]

PMID: 29309602

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Project description:The Venus kinase receptor (VKR) is a single transmembrane molecule composed of an intracellular tyrosine kinase domain close to that of insulin receptor and an extracellular Venus Flytrap (VFT) structure similar to the ligand binding domain of many class C G protein coupled receptors. This receptor tyrosine kinase (RTK) was first discovered in the platyhelminth parasite Schistosoma mansoni, then in a large variety of invertebrates. A single vkr gene is found in most genomes, except in S. mansoni in which two genes Smvkr1 and Smvkr2 exist. VKRs form a unique family of RTKs present only in invertebrates and their biological functions are still to be discovered. In this work, we show that SmVKRs are expressed in the reproductive organs of S. mansoni, particularly in the ovaries of female worms. By transcriptional analyses evidence was obtained that both SmVKRs fulfill different roles during oocyte maturation. Suppression of Smvkr expression by RNA interference induced spectacular morphological changes in female worms with a strong disorganization of the ovary, which was dominated by the presence of primary oocytes, and a defect of egg formation. Following expression in Xenopus oocytes, SmVKR1 and SmVKR2 receptors were shown to be activated by distinct ligands which are L-Arginine and calcium ions, respectively. Signalling analysis in Xenopus oocytes revealed the capacity of SmVKRs to activate the PI3K/Akt/p70S6K and Erk MAPK pathways involved in cellular growth and proliferation. Additionally, SmVKR1 induced phosphorylation of JNK (c-Jun N-terminal kinase). Activation of JNK by SmVKR1 was supported by the results of yeast two-hybrid experiments identifying several components of the JNK pathway as specific interacting partners of SmVKR1. In conclusion, these results demonstrate the functions of SmVKR in gametogenesis, and particularly in oogenesis and egg formation. By eliciting signalling pathways potentially involved in oocyte proliferation, growth and migration, these receptors control parasite reproduction and can therefore be considered as potential targets for anti-schistosome therapies.

Dataset Information

Glucose Uptake in the Human Pathogen Schistosoma mansoni Is Regulated Through Akt/Protein Kinase B Signaling.

Publications

Glucose Uptake in the Human Pathogen Schistosoma mansoni Is Regulated Through Akt/Protein Kinase B Signaling.

Similar Datasets

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