Characterisation of the Chloroquine Resistance Transporter homologue in Toxoplasma

Eukaryot Cell. 2014 May 23. pii: EC.00027-14. [Epub ahead of print]

Characterisation of the Chloroquine Resistance Transporter homologue in Toxoplasma gondii

Warring SD¹, Dou Z², Carruthers VB², McFadden GI¹, van Dooren GG³.

Abstract

Mutations in the Plasmodium falciparum chloroquine resistance transporter (PfCRT) protein confer resistance to the anti-malarial drug chloroquine. PfCRT localises to the parasite digestive vacuole, the site of chloroquine action, where it mediates resistance by transporting chloroquine out of the digestive vacuole. PfCRT belongs to a family of transporter proteins called the chloroquine resistance transporter (CRT) family. CRT family proteins are found throughout the Apicomplexa, in some protists and in plants. Despite the importance of PfCRT in drug resistance, little is known about the evolution or native function of CRT proteins. The apicomplexan parasite Toxoplasma gondii contains one CRT family protein. We demonstrate that T. gondii CRT (TgCRT) co-localizes with markers for the vacuolar compartment (VAC) in these parasites. The TgCRT-containing VAC is a highly dynamic organelle, changing morphology and protein composition between intracellular and extracellular forms of the parasite. Regulated knockdown of TgCRT expression resulted in modest reduction in parasite fitness and swelling of the VAC, indicating that TgCRT contributes to parasite growth and VAC physiology. Together, our findings provide new information on the role of CRT-family proteins in apicomplexan parasites.
Copyright © 2014, American Society for Microbiology. All Rights Reserved.

PMID:

24859994

[PubMed - as supplied by publisher]