Openly accessible

Investigation of the plasmodium falciparum food vacuole through inducible expression of the chloroquine resistance transporter (PfCRT)

Ehlgen, Florian, Pham, James S., de Koning-Ward, Tania, Cowman, Alan F. and Ralph, Stuart A. 2012, Investigation of the plasmodium falciparum food vacuole through inducible expression of the chloroquine resistance transporter (PfCRT), PLoS One, vol. 7, no. 6.

Attached Files
Name Description MIMEType Size Downloads
koningward-investigationof-2012.pdf Published version application/pdf 2.26MB 23

Title Investigation of the plasmodium falciparum food vacuole through inducible expression of the chloroquine resistance transporter (PfCRT)
Author(s) Ehlgen, Florian
Pham, James S.
de Koning-Ward, Tania
Cowman, Alan F.
Ralph, Stuart A.
Journal name PLoS One
Volume number 7
Issue number 6
Total pages 12
Publisher Public Library of Science
Place of publication San Francisco, Calif.
Publication date 2012-06-13
ISSN 1932-6203
Keyword(s) brefeldin A
chloroquine
chloroquine resistance transporter
dynamin
green fluorescent protein
hemozoin
membrane protein
unclassified drug
Summary Haemoglobin degradation during the erythrocytic life stages is the major function of the food vacuole (FV) of Plasmodium falciparum and the target of several anti-malarial drugs that interfere with this metabolic pathway, killing the parasite. Two multi-spanning food vacuole membrane proteins are known, the multidrug resistance protein 1 (PfMDR1) and Chloroquine Resistance Transporter (PfCRT). Both modulate resistance to drugs that act in the food vacuole. To investigate the formation and behaviour of the food vacuole membrane we have generated inducible GFP fusions of chloroquine sensitive and resistant forms of the PfCRT protein. The inducible expression system allowed us to follow newly-induced fusion proteins, and corroborated a previous report of a direct trafficking route from the ER/Golgi to the food vacuole membrane. These parasites also allowed the definition of a food vacuole compartment in ring stage parasites well before haemozoin crystals were apparent, as well as the elucidation of secondary PfCRT-labelled compartments adjacent to the food vacuole in late stage parasites. We demonstrated that in addition to previously demonstrated Brefeldin A sensitivity, the trafficking of PfCRT is disrupted by Dynasore, a non competitive inhibitor of dynamin-mediated vesicle formation. Chloroquine sensitivity was not altered in parasites over-expressing chloroquine resistant or sensitive forms of the PfCRT fused to GFP, suggesting that the PfCRT does not mediate chloroquine transport as a GFP fusion protein.
Language eng
Field of Research 060599 Microbiology not elsewhere classified
060108 Protein Trafficking
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2012, Public Library of Science
Persistent URL http://hdl.handle.net/10536/DRO/DU:30050405

Document type: Journal Article
Collections: School of Medicine
Open Access Collection
Connect to link resolver
 
Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved.

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.

Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 3 times in TR Web of Science
Scopus Citation Count Cited 5 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 31 Abstract Views, 24 File Downloads  -  Detailed Statistics
Created: Tue, 05 Feb 2013, 11:14:57 EST by Jane Moschetti

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.