The <i>Plasmodium falciparum</i> homolog of Vps16 interacts with the core members of the Vps-C tethering complex
Notice bibliographique
Résumé
ABSTRACT The organelles of the apical complex (rhoptries, micronemes, and dense granules) are critical for erythrocyte invasion by the malaria parasite Plasmodium falciparum . Though they have essential roles in the parasite lifecycle, the mechanisms behind their biogenesis are still poorly defined. The Class C Vps proteins Vps11, Vps16, Vps18, and Vps33 constitute the core of the CORVET and HOPS complexes implicated in vesicle tethering and fusion in the eukaryotic endolysosomal system. Work in the model apicomplexan Toxoplasma gondii has revealed that TgVps11 is essential for the generation of the apical complex. P. falciparum possesses all four subunits of the Vps-C complex, and recent work has shown that some of its components were critical for host-cell cytosol trafficking and the biogenesis of the apical complex. We here show that the P. falciparum ortholog of Vps16, a member of the Vps-C complex, is expressed throughout the asexual erythrocytic cycle and that it is potentially associated with the Golgi apparatus and the rhoptries in schizont stage parasites. We then demonstrate by immunoprecipitation and mass spectrometry that PfVps16 interacts with all the members of the canonical Vps-C complex along with the Vps3 CORVET component. Interestingly, three uncharacterized Plasmodium -specific proteins are also found as interactors of PfVps16, and structural predictions revealed that two of them possess folds commonly found in proteins present in membrane tethering complexes. These findings suggest that P. falciparum may possess both conserved and parasite-specific features within its endosomal tethering machinery. IMPORTANCE The malaria parasite relies on special compartments to invade red blood cells. These are key to the parasite’s ability to infect, but how these are generated is not well known. In eukaryotic cells, certain protein assemblies, called tethering complexes, help move and fuse small transport vesicles, which is important for building and maintaining organelles. Plasmodium falciparum possesses some of these proteins, and recent studies suggest they play an important role in building its infection machinery and transporting material inside the parasite. We found that the malaria parasite possesses additional components associated with the typical tethering proteins and that these are not found in other eukaryotes. These results suggest that P. falciparum uses both common and unique tools to create the cellular machinery it needs to infect red blood cells. We propose that the Plasmodium -specific components might represent interesting targets for the development of antimalarials with potentially reduced side effects since they are not present in humans.
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Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| 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) | 0,000 | 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 tête enseignante, 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 ».