Identification of the glycosylphosphatidylinositol-specific phospholipase A2 (GPI-PLA2) of GPI fatty acid remodelling inTrypanosoma brucei
Author:
Ji Zhe,Nagar Rupa,Duncan Samuel M.,Sampaio Guther Maria Lucia,Ferguson Michael A.J.
Abstract
AbstractThe biosynthesis of glycosylphosphatidylinositol (GPI) anchored proteins (GPI-APs) in the parasitic protozoanTrypanosoma bruceiinvolves fatty acid remodelling of the GPI precursor molecules before they are transferred to protein in the endoplasmic reticulum. The genes encoding the requisite phospholipase A2 and A1 activities for this remodelling have thus far been elusive. Here, we identify a gene, Tb927.7.6110, that encodes a protein that is necessary and sufficient for GPI-phospholipase A2 (GPI-PLA2) activity in the procyclic form of the parasite. The predicted protein product belongs to the alkaline ceramidase, PAQR receptor, Per1, SID-1, and TMEM8 (CREST) superfamily of transmembrane hydrolase proteins and shows sequence similarity to Post-GPI-Attachment to Protein 6 (PGAP6), a GPI-PLA2 that acts after transfer of GPI precursors to protein in mammalian cells. The trypanosome Tb927.7.6110 GPI-PLA2 gene resides in a locus with two closely related genes Tb927.7.6150 and Tb927.7.6170, one of which (Tb927.7.6150) most likely encodes a catalytically inactive protein. The absence of GPI-PLA2 in the null mutant procyclic cells not only affected fatty acid remodelling but also reduced GPI anchor sidechain size on mature GPI-anchored procyclin glycoproteins. This reduction in GPI anchor sidechain size was reversed upon the add back of Tb927.7.6110 and of Tb927.7.6170, despite the latter not encoding GPI precursor GPI-PLA2 activity.
Publisher
Cold Spring Harbor Laboratory
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