Rab7 of Plasmodium falciparum is involved in its retromer complex assembly near the digestive vacuole.
Antimalarials
/ pharmacology
Chloroquine
/ pharmacology
Humans
Magnesium
/ metabolism
Malaria, Falciparum
/ drug therapy
Models, Molecular
Plasmodium falciparum
/ drug effects
Protein Interaction Maps
/ drug effects
Vacuoles
/ drug effects
rab GTP-Binding Proteins
/ metabolism
rab7 GTP-Binding Proteins
Digestive vacuole
GTPase
Plasmodium falciparum
Rab7
Retromer complex
Journal
Biochimica et biophysica acta. General subjects
ISSN: 1872-8006
Titre abrégé: Biochim Biophys Acta Gen Subj
Pays: Netherlands
ID NLM: 101731726
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
24
01
2020
revised:
22
04
2020
accepted:
02
06
2020
pubmed:
9
6
2020
medline:
15
12
2020
entrez:
9
6
2020
Statut:
ppublish
Résumé
Intracellular protein trafficking is crucial for survival of cell and proper functioning of the organelles; however, these pathways are not well studied in the malaria parasite. Its unique cellular architecture and organellar composition raise an interesting question to investigate. The interaction of Plasmodium falciparum Rab7 (PfRab7) with vacuolar protein sorting-associated protein 26 (PfVPS26) of retromer complex was shown by coimmunoprecipitation (co-IP). Confocal microscopy was used to show the localization of the complex in the parasite with respect to different organelles. Further chemical tools were employed to explore the role of digestive vacuole (DV) in retromer trafficking in parasite and GTPase activity of PfRab7 was examined. PfRab7 was found to be interacting with retromer complex that assembled mostly near DV and the Golgi in trophozoites. Chemical disruption of DV by chloroquine (CQ) led to its disassembly that was further validated by using compound 5f, a heme polymerization inhibitor in the DV. PfRab7 exhibited Mg Retromer complex was found to be interacting with PfRab7 and the functional integrity of the DV was found to be important for retromer assembly in P. falciparum. This study explores the retromer trafficking in P. falciparum and describes amechanism to validate DV targeting antiplasmodial molecules.
Sections du résumé
BACKGROUND
Intracellular protein trafficking is crucial for survival of cell and proper functioning of the organelles; however, these pathways are not well studied in the malaria parasite. Its unique cellular architecture and organellar composition raise an interesting question to investigate.
METHODS
The interaction of Plasmodium falciparum Rab7 (PfRab7) with vacuolar protein sorting-associated protein 26 (PfVPS26) of retromer complex was shown by coimmunoprecipitation (co-IP). Confocal microscopy was used to show the localization of the complex in the parasite with respect to different organelles. Further chemical tools were employed to explore the role of digestive vacuole (DV) in retromer trafficking in parasite and GTPase activity of PfRab7 was examined.
RESULTS
PfRab7 was found to be interacting with retromer complex that assembled mostly near DV and the Golgi in trophozoites. Chemical disruption of DV by chloroquine (CQ) led to its disassembly that was further validated by using compound 5f, a heme polymerization inhibitor in the DV. PfRab7 exhibited Mg
CONCLUSION
Retromer complex was found to be interacting with PfRab7 and the functional integrity of the DV was found to be important for retromer assembly in P. falciparum.
GENERAL SIGNIFICANCE
This study explores the retromer trafficking in P. falciparum and describes amechanism to validate DV targeting antiplasmodial molecules.
Identifiants
pubmed: 32512169
pii: S0304-4165(20)30168-9
doi: 10.1016/j.bbagen.2020.129656
pii:
doi:
Substances chimiques
Antimalarials
0
rab7 GTP-Binding Proteins
0
rab7 GTP-binding proteins, human
0
Chloroquine
886U3H6UFF
rab GTP-Binding Proteins
EC 3.6.5.2
Magnesium
I38ZP9992A
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
129656Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare no conflict of interest associated with this publication.