A novel ATP-binding cassette transporter from Leishmania is involved in transport of phosphatidylcholine analogues and resistance to alkyl-phospholipids
A novel ATP-binding cassette transporter from Leishmania is involved in transport of phosphatidylcholine analogues and resistance to alkyl-phospholipids
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DOI：
10.1111/j.1365-2958.2007.05653.x
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发表时间：
2007-06-01
影响因子：
3.6
通讯作者：
Castanys, Santiago
中科院分区：
文献类型：
--
作者：
Castanys-Munoz, Esther;Alder-Baerens, Nele;Castanys, Santiago
atp结合盒（ABC）转运蛋白是一个重要的膜蛋白家族，参与耐药和其他生物活动。本文报道了利什曼原虫中首个ABC亚家族G （ABCG）样转运蛋白LiABCG4的特征。LiABCG4主要定位于寄生虫的质膜。这种半转运体的过度表达减少了磷脂酰胆碱类似物的积累，并赋予了对烷基磷脂的抗性。同样，当在酿酒酵母中表达时，该蛋白定位于酵母质膜并赋予对烷基磷脂的抗性。从过表达liabcg4的酵母突变体中分离出的高尔基分泌后囊泡含有利什曼ABC转运蛋白，并表现出atp依赖、钒酸盐敏感的磷脂酰胆碱类似物从胞质转运到囊泡膜的管腔小叶。交联显示LiABCG4的二聚化。这些结果表明，LiABCG4参与了利什曼原虫磷脂酰胆碱的主动转运和对烷基磷脂的抗性。
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.