title: Plasmenylethanolamine synthesis in Leishmania major.
abstract: Ethanolamine glycerophospholipids are ubiquitous cell membrane components. Trypanosomatid parasites of the genus Leishmania synthesize the majority of their ethanolamine glycerophospholipids as 1-O-alk-1'-enyl-2-acyl-sn-glycero-3-phosphoethanolamine or plasmenylethanolamine (PME) through the Kennedy pathway. PME is a subtype of ether phospholipids also known as ethanolamine plasmalogen whose functions are not well characterized. In this study, we investigated the role of PME synthesis in Leishmania major through the characterization of an ethanolamine phosphotransferase (EPT) mutant. EPT-null parasites are largely devoid of PME and fully viable in regular medium but fail to proliferate in the absence of fetal bovine serum. They exhibit significant abnormalities in the synthesis and localization of GPI-anchored surface molecules. EPT-null mutants also show attenuated virulence in BALB/c mice. Furthermore, in addition to PME synthesis, ethanolamine also contributes to the production of phosphatidylcholine, the most abundant class of lipids in Leishmania. Together, these findings suggest that ethanolamine production is likely required for Leishmania promastigotes to generate bulk phospholipids, to handle stress, and to control the expression of membrane bound virulence factors.
authors.affiliation: Department of Biological Sciences, Texas Tech University, Lubbock, TX, 79409, USA.
authors.forename: Mattie C
authors.initials: MC
authors.lastname: Pawlowic
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine, 660 S. Euclid Ave., Saint Louis, MO, 63110, USA.
authors.forename: Fong-Fu
authors.initials: FF
authors.lastname: Hsu
authors.affiliation: Department of Biological Sciences, Texas Tech University, Lubbock, TX, 79409, USA.
authors.forename: Samrat
authors.initials: S
authors.lastname: Moitra
authors.affiliation: Department of Biological Sciences, Texas Tech University, Lubbock, TX, 79409, USA.
authors.forename: Neha
authors.initials: N
authors.lastname: Biyani
authors.affiliation: Department of Biological Sciences, Texas Tech University, Lubbock, TX, 79409, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
mesh_terms: D000818:Animals; D019856:Ethanolamine / Q000378:metabolism; D004982:Ethanolaminephosphotransferase / Q000378:metabolism; D004983:Ethanolamines / Q000378:metabolism; D005260:Female; D018320:Leishmania major / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D010955:Plasmalogens / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D004983:Ethanolamines; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D010955:Plasmalogens; C020791:phosphatidal ethanolamines; D019856:Ethanolamine; C005448:phosphorylethanolamine; D004982:Ethanolaminephosphotransferase