1. A novel ATP-binding cassette transporter from Leishmania is involved in transport of phosphatidylcholine analogues and resistance to alkyl-phospholipids
- Author
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Thomas Günther Pomorski, Santiago Castanys, Nele Alder-Baerens, Francisco Gamarro, and Esther Castanys-Muñoz
- Subjects
biology ,Saccharomyces cerevisiae ,Phospholipid ,ATP-binding cassette transporter ,Transporter ,biology.organism_classification ,Microbiology ,Secretory Vesicle ,Cytosol ,chemistry.chemical_compound ,chemistry ,Biochemistry ,Membrane protein ,Phosphatidylcholine ,lipids (amino acids, peptides, and proteins) ,Molecular Biology - Abstract
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.
- Published
- 2007