title: Leishmania dihydroxyacetonephosphate acyltransferase LmDAT is important for ether lipid biosynthesis but not for the integrity of detergent resistant membranes.
abstract: Glycerolipid biosynthesis in Leishmania initiates with the acylation of glycerol-3-phosphate by a single glycerol-3-phosphate acyltransferase, LmGAT, or of dihydroxyacetonephosphate by a dihydroxyacetonephosphate acyltransferase, LmDAT. We previously reported that acylation of the precursor dihydroxyacetonephosphate rather than glycerol-3-phosphate is the physiologically relevant pathway for Leishmania parasites. We demonstrated that LmDAT is important for normal growth, survival during the stationary phase, and for virulence. Here, we assessed the role of LmDAT in glycerolipid metabolism and metacyclogenesis. LmDAT was found to be implicated in the biosynthesis of ether glycerolipids, including the ether lipid derived virulence factor lipophosphoglycan and glycosylphosphatidylinositol-anchored proteins. The null mutant produced longer lipophosphoglycan molecules that were not released in the medium, and augmented levels of glycosylphosphatidylinositol-anchored proteins. In addition, the integrity of detergent resistant membranes was not affected by the absence of the LmDAT gene. Further, our genetic analyses strongly suggest that LmDAT was synthetic lethal with the glycerol-3-phosphate acyltransferase encoding gene LmGAT, implying that Leishmania expresses only two acyltransferases that initiate the biosynthesis of its cellular glycerolipids. Last, despite the fact that LmDAT is important for virulence the null mutant still exhibited the typical characteristics of metacyclics.
authors.affiliation: Department of Biological Sciences, St John's University, 8000 Utopia Parkway, Jamaica, NY 11439, USA. zufferer@stjohns.edu
authors.forename: Rachel
authors.initials: R
authors.lastname: Zufferey
authors.forename: Gada K
authors.initials: GK
authors.lastname: Al-Ani
authors.forename: Kara
authors.initials: K
authors.lastname: Dunlap
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects*; D003902:Detergents / Q000494:pharmacology*; D004986:Ether / Q000378:metabolism*; D017353:Gene Deletion; D007891:Leishmania / Q000187:drug effects / Q000201:enzymology*; D008055:Lipids / Q000096:biosynthesis*
chemical_list: D003902:Detergents; D008055:Lipids; D004986:Ether; D000217:Acyltransferases; C020051:glycerone-phosphate O-acyltransferase