Plasmodium falciparum chloroquine resistance transporter (PfCRT) (PfCRT)

Plasmodium falciparum chloroquine resistance transporter (PfCRT) is a 424-amino acid transmembrane protein located in the membrane of the malaria parasite's digestive vacuole [UniProt: Q9N600]. Its primary physiological function is believed to be the transport of amino acids or peptides, products of hemoglobin digestion, out of the vacuole to maintain osmotic balance and provide nutrients to the parasite [PubMed: 21167024]. PfCRT is the central mediator of resistance to chloroquine, a once-mainstay antimalarial treatment. Mutations in the pfcrt gene, most notably the K76T substitution, transform the transporter into a conduit that allows the efflux of diprotonated chloroquine from the acidic vacuole into the parasite's cytoplasm [PubMed: 10846171]. This efflux prevents chloroquine from reaching the concentrations necessary to inhibit the polymerization of toxic heme into inert hemozoin, thereby allowing the parasite to survive drug exposure. PfCRT is considered a high-priority target for the development of chemosensitizers or resistance-breakers that can inhibit the efflux mechanism and restore the clinical utility of 4-aminoquinoline drugs [PubMed: 15522127].

Other names

Chloroquine resistance proteinCRTPfCRTChloroquine efflux pumpTransporter protein CRT

Mutated PfCRT facilitates the efflux of chloroquine from the parasite's digestive vacuole, reducing the drug's concentration at its site of action where it normally inhibits heme polymerization [PubMed: 10846171, 21167024].