title: Characterization of the chloroquine resistance transporter homologue in Toxoplasma gondii.
abstract: Mutations in the Plasmodium falciparum chloroquine resistance transporter (PfCRT) protein confer resistance to the antimalarial drug chloroquine. PfCRT localizes 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 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) colocalizes with markers for the vacuolar (VAC) compartment in these parasites. The TgCRT-containing VAC is a highly dynamic organelle, changing its 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.
authors.affiliation: Plant Cell Biology Research Centre, School of Botany, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Sally D
authors.initials: SD
authors.lastname: Warring
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Dou
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Vern B
authors.initials: VB
authors.lastname: Carruthers
authors.affiliation: Plant Cell Biology Research Centre, School of Botany, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Geoffrey I
authors.initials: GI
authors.lastname: McFadden
authors.affiliation: Research School of Biology, Australian National University, Canberra, Australia giel.vandooren@anu.edu.au.
authors.forename: Giel G
authors.initials: GG
authors.lastname: van Dooren
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D001483:Base Sequence; D001692:Biological Transport / Q000235:genetics*; D002738:Chloroquine / Q000494:pharmacology*; D004351:Drug Resistance; D055786:Gene Knockout Techniques; D026901:Membrane Transport Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics*; D016415:Sequence Alignment; D014122:Toxoplasma / Q000378:metabolism*
chemical_list: D000962:Antimalarials; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D002738:Chloroquine