Identification of a serotonin transporter and serotonin receptor in «Schistosoma mansoni»: a step towards better understanding the serotonergic system
Notice bibliographique
Résumé
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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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».