A novel ATP-binding cassette transporter from Leishmania is involved in transport of phosphatidylcholine analogues and resistance to alkyl-phospholipids.
ATP-binding cassette (ABC) transporters represent an important family of membrane proteins involved in drug resistance and other biological activities. The present work reports the characterization of the first ABC subfamily G (ABCG)-like transporter, LiABCG4, in the protozoan parasite Leishmania. LiABCG4 localized mainly to the parasite plasma membrane. Overexpression of this half-transporter reduced the accumulation of phosphatidylcholine analogues and conferred resistance to alkyl-phospholipids. Likewise, when expressed in Saccharomyces cerevisiae, the protein localized to the yeast plasma membrane and conferred resistance to alkyl-phospholipids. Post-Golgi secretory vesicles isolated from a LiABCG4-overexpressing yeast mutant contained the leishmanial ABC transporter and exhibited ATP-dependent, vanadate-sensitive transport of phosphatidylcholine analogues from the cytosolic to the lumenal leaflet of the vesicle membrane. Cross-linking showed dimerization of LiABCG4. These results suggest that LiABCG4 is involved in the active transport of phosphatidylcholine and resistance to alkyl-phospholipids in Leishmania.
Castanys-Muñoz
Esther
E
Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Parque Tecnológico de Ciencias de la Salud, Avda. del Conocimiento s/n, 18100 Armilla, Granada, Spain. casatanys@ipb.csic.es
Alder-Baerens
Nele
N
Pomorski
Thomas
T
Gamarro
Francisco
F
Castanys
Santiago
S
D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018314:Leishmania infantum / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism*; D010742:Phospholipid Ethers / Q000378:metabolism* / Q000494:pharmacology; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000235:genetics; D014170:Transformation, Genetic
D018528:ATP-Binding Cassette Transporters; D000981:Antiprotozoal Agents; D010713:Phosphatidylcholines; D010742:Phospholipid Ethers; D010767:Phosphorylcholine; D049452:Green Fluorescent Proteins; C026659:edelfosine; C105905:perifosine; C039128:miltefosine