Plasmodium falciparum chloroquine resistance transporter is a H+-coupled polyspecific nutrient and drug exporter.
Extrusion of chloroquine (CQ) from digestive vacuoles through the Plasmodium falciparum CQ resistance transporter (PfCRT) is essential to establish CQ resistance of the malaria parasite. However, the physiological relevance of PfCRT and how CQ-resistant PfCRT gains the ability to transport CQ remain unknown. We prepared proteoliposomes containing purified CQ-sensitive and CQ-resistant PfCRTs and measured their transport activities. All PfCRTs tested actively took up tetraethylammonium, verapamil, CQ, basic amino acids, polypeptides, and polyamines at the expense of an electrochemical proton gradient. CQ-resistant PfCRT exhibited decreased affinity for CQ, resulting in increased CQ uptake. Furthermore, CQ competitively inhibited amino acid transport. Thus, PfCRT is a H(+)-coupled polyspecific nutrient and drug exporter.
Advanced Science Research Center, Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Tokyo 113-8656, Japan; and.
Narinobu
N
Juge
Department of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan;
Sawako
S
Moriyama
Advanced Science Research Center.
Takaaki
T
Miyaji
Department of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan;
Mamiyo
M
Kawakami
Department of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan;
Haruka
H
Iwai
Department of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan;
Tomoya
T
Fukui
Department of Biochemistry, the George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
Nathan
N
Nelson
Department of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan; moriyama@pheasant.pharm.okayama-u.ac.jp omote@pheasant.pharm.okayama-u.ac.jp.
Hiroshi
H
Omote
Advanced Science Research Center, Department of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan; moriyama@pheasant.pharm.okayama-u.ac.jp omote@pheasant.pharm.okayama-u.ac.jp.
Yoshinori
Y
Moriyama
D000596:Amino Acids / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology; D004351:Drug Resistance / Q000187:drug effects; D026901:Membrane Transport Proteins / Q000378:metabolism*; D011522:Protons; D015800:Protozoan Proteins / Q000378:metabolism*; D019789:Tetraethylammonium / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D000596:Amino Acids; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D011522:Protons; D015800:Protozoan Proteins; D019789:Tetraethylammonium; D002738:Chloroquine; D014700:Verapamil
amino acid; chloroquine; malaria; pfcrt; transporter