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A novel ATP‐binding cassette transporter from Leishmania is involved in transport of phosphatidylcholine analogues and resistance to alkyl‐phospholipids
Author(s) -
CastanysMuñoz Esther,
AlderBaerens Nele,
Pomorski Thomas,
Gamarro Francisco,
Castanys Santiago
Publication year - 2007
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2007.05653.x
Subject(s) - atp binding cassette transporter , biology , phosphatidylcholine , leishmania , biochemistry , transporter , vesicle , vesicular transport proteins , flippase , vesicular transport protein , leishmania mexicana , membrane transport protein , microbiology and biotechnology , phosphatidylserine , membrane protein , saccharomyces cerevisiae , yeast , membrane , phospholipid , parasite hosting , gene , vacuolar protein sorting , world wide web , computer science
Summary 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.