ShAR1α and ShAR1β: novel putative nicotinic acetylcholine receptor subunits from the platyhelminth blood fluke Schistosoma

Bentley, Geoffrey N.; Jones, Andrew K.; Parra, William G Oliveros; Agnew, Alison

doi:10.1016/j.gene.2003.12.009

Cited by 34 publications

(37 citation statements)

References 39 publications

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“…It has been reported that S. haematobium AChR1α is located on the parasite surface and may contribute to the potentiation of the uptake of glucose from host blood in response to circulating concentrations of ACh [25], whereas AChR1β is distributed within the musculature and on discrete cell bodies within the connective parenchyma [25]. The depressed expression of AChR1α in both fragmented and intact adult S. japonicum with knock-down of SjAChE , indicated the close relationship between AChE and AChR1α, both of which are located in/on the membrane surface of schistosomes and are associated with its transporting function in nutrient transport.…”

Section: Discussionmentioning

confidence: 99%

Suppression of Schistosoma japonicum Acetylcholinesterase Affects Parasite Growth and Development

You

Liu

et al. 2018

IJMS

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To further investigate the importance of Schistosoma japonicum acetylcholinesterase (SjAChE) in cholinergic signaling for parasite growth and development, we used RNA interference (RNAi) to knock-down its expression in adults and eggs in vitro. This resulted in its reduced transcription but also expression of other important genes involved both in cholinergic signaling and glucose uptake were impacted substantially. Significant decreases in AChE protein expression, AChE enzymatic activity, and glucose uptake were observed in the SjAChE-knockdown parasites compared with luciferase controls. In vaccine/challenge experiments, we found that immunization of mice with recombinant SjAChE (rSjAChE) expressed in Escherichia coli elicited reductions in male worm numbers (33%), liver granuloma density (41%), and reduced numbers of mature intestinal eggs (73%) in the vaccinated group compared with the control group. These results indicate AChE plays an important role in the metabolism of male worms, and impacts indirectly on female fecundity leading to increased numbers of immature eggs being released and reduced sizes of liver granulomas. Furthermore, cytokine analysis showed that immunization of mice with rSjAChE elicited a predominantly Th1-type immune response characterized by increased production of IFNγ in splenic CD4+ T cells of vaccinated mice. The study confirms the potential of SjAChE as a vaccine/drug candidate against zoonotic schistosomiasis japonica.

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Section: Discussionmentioning

confidence: 99%

Suppression of Schistosoma japonicum Acetylcholinesterase Affects Parasite Growth and Development

You

Liu

et al. 2018

IJMS

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“…The remaining 5k and 3k ends were subsequently obtained directly from a cDNA library by anchored PCR using sequence-specific and vector-derived primers. Initially cloned from S. haematobium, virtually identical nAChR sequences were subsequently obtained from S. mansoni and S. bovis (Bentley et al 2004). A sequence alignment of the schistosome sequences with other LGICs identified the conserved 13 residue Cys-loop motif and a typical topology of the Cys-loop family.…”

Section: Nicotinic (Acetylcholine) Ionotropic Receptorsmentioning

confidence: 99%

“…Co-expression of ShAR1a with a vertebrate b subunit also failed to produce a response as did the expression of a chimeric form of ShAR1a that contained the M3-M4 region (second intracellular loop) of vertebrate a7. In contrast, expression of the wildtype a7 orthologue produced a fully functional homomeric channel (Bentley et al 2004). It is unknown if the lack of ShAR1 activity was due to problems related to heterologous expression in the oocytes, or because the required subunit partners for ShAR1a and ShAR1b have yet to be discovered.…”

Section: Nicotinic (Acetylcholine) Ionotropic Receptorsmentioning

confidence: 99%

Classical transmitters and their receptors in flatworms

2006

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The flatworm nervous system employs a wide repertoire of neuroactive substances, including small chemical messengers, the so called classical transmitters, and several types of neuropeptides. A large body of research accumulated over four decades has provided a wealth of information on the tissue localization and effects of these substances, their biochemistry and, recently, their molecular modes of action in all major classes of flatworms. This evidence will be reviewed, with particular emphasis on the small (classical) transmitters and the receptors that mediate their effects. One of the themes that will emerge from this discussion is that classical transmitters regulate core activities such as movement, metabolism and transport, and thus are essential for survival of the organism. In addition, the evidence shows that flatworms have multiple neurotransmitter receptors, many with unusual pharmacological features, which make them particularly attractive as drug targets. Understanding the molecular basis of these distinctive properties, and developing new, more specific receptor agonists and antagonists will undoubtedly become a major challenge in future research.

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“…Schistosomes have several putative ACh receptors that may be responsible for this phenomenon [reviewed in 7]. The majority of these receptors are nicotinic ion channels, some of which have been cloned and characterized in vitro [21, 22]. However, two muscarinic cholinergic receptors are also predicted.…”

Section: Introductionmentioning

confidence: 99%

A constitutively active G protein-coupled acetylcholine receptor regulates motility of larval Schistosoma mansoni

MacDonald

Kimber

Day

et al. 2015

Molecular and Biochemical Parasitology

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The neuromuscular system of helminths controls a variety of essential biological processes and therefore represents a good source of novel drug targets. The neuroactive substance, acetylcholine controls movement of Schistosoma mansoni but the mode of action is poorly understood. Here, we present first evidence of a functional G protein-coupled acetylcholine receptor in S. mansoni, which we have named SmGAR. A bioinformatics analysis indicated that SmGAR belongs to a clade of invertebrate GAR-like receptors and is related to vertebrate muscarinic acetylcholine receptors. Functional expression studies in yeast showed that SmGAR is constitutively active but can be further activated by acetylcholine and, to a lesser extent, the cholinergic agonist, carbachol. Anti-cholinergic drugs, atropine and promethazine, were found to have inverse agonist activity towards SmGAR, causing a significant decrease in the receptor’s basal activity. An RNAi phenotypic assay revealed that suppression of SmGAR activity in early-stage larval schistosomulae leads to a drastic reduction in larval motility. In sum, our results provide the first molecular evidence that cholinergic GAR -like receptors are present in schistosomes and are required for proper motor control in the larvae. The results further identify SmGAR as a possible candidate for antiparasitic drug targeting.

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ShAR1α and ShAR1β: novel putative nicotinic acetylcholine receptor subunits from the platyhelminth blood fluke Schistosoma

Cited by 34 publications

References 39 publications

Suppression of Schistosoma japonicum Acetylcholinesterase Affects Parasite Growth and Development

Suppression of Schistosoma japonicum Acetylcholinesterase Affects Parasite Growth and Development

Classical transmitters and their receptors in flatworms

A constitutively active G protein-coupled acetylcholine receptor regulates motility of larval Schistosoma mansoni

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