Identification of a serotonin transporter and serotonin receptor in «Schistosoma mansoni»: a step towards better understanding the serotonergic system
Bibliographic record
Abstract
Among the top list of neglected tropical diseases sits schistosomiasis, a parasitic disease caused by the flatworm Schistosoma. The disease involves an intermediate snail host and the definitive human host with infection taking place through the skin in contaminated water, one of the reasons for its wide distribution. The diversity of the life cycle stages and the ability of the parasite to have adapted to quite different environments speak to the complexity of the organism. The underlying system that coordinates and controls all biological functions of the parasite is its nervous system. Signalling in the nervous system is accomplished by the release of neurotransmitters and signal transduction through specific receptors. Of the many neurotransmitters identified thus far in the parasite, serotonin (5-hydroxytryptamine: 5HT) is one of the most abundant. 5HT has been implicated in several biological functions in flatworms, including muscle contraction, motility and metabolism, but its mode of action is poorly understood. Here we provide molecular evidence for a serotonin-specific transporter (SERT) in Schistosoma mansoni as well as a serotonin specific receptor in the same organism. The transporter (SmSERT) was shown to share similar topology to SERTs from other organisms, namely 12 transmembrane regions with several predicted glycosylation sites. In a heterologous expression system, we show that it mediates the uptake of serotonin in a dose-dependent manner and is responsive to classical SERT inhibitors. The transporter is expressed in all life cycle stages tested (cercaria, schistosomulum, and adult) with upregulation occurring in the parasitic stages. Immunolocalization studies showed that the protein is expressed primarily in the nervous system of the parasite, both in central and peripheral neuronal structures. Using RNA interference (RNAi) to knockdown expression, we found strong increases in motility, suggesting that its primary function is in termination of serotonin signalling. The serotonin receptor (Sm5HTr) is the first as such cloned from parasitic flatworms. It shares homology with other 5HT receptors and most closely identifies with the 5HT7 class of receptors. Expression in mammalian cells found that it signals through upregulation of cAMP and not Ca2+. Immunolocalization in adults and larvae found that the receptor is enriched in the central and peripheral nervous system. Additional pharmacological assays using Sm5HTr agonists and antagonists suggest that the receptor may contribute to 5HT-induced stimulation of worm motility. Combined, these results show that there is a fully functional serotonergic system in the parasite S. mansoni and that these proteins play an important role in controlling signal transduction. The wide distribution of these proteins in the parasite nervous system and their apparent involvement in motor control makes them tempting targets for drug design.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".