Phosphatidylethanolamine Is the Precursor of the Ethanolamine Phosphoglycerol Moiety Bound to Eukaryotic Elongation Factor 1A

Abstract

In addition to its conventional role during protein synthesis, eukaryotic elongation factor 1A is involved in other cellular processes. Several regions of interaction between eukaryotic elongation factor 1A and the translational apparatus or the cytoskeleton have been identified, yet the roles of the different post-translational modifications of eukaryotic elongation factor 1A are completely unknown. One amino acid modification, which so far has only been found in eukaryotic elongation factor 1A, consists of ethanolamine-phosphoglycerol attached to two glutamate residues that are conserved between mammals and plants. We now report that ethanolamine-phosphoglycerol is also present in eukaryotic elongation factor 1A of the protozoan parasite Trypanosoma brucei, indicating that this unique protein modification is of ancient origin. In addition, using RNA-mediated gene silencing against enzymes of the Kennedy pathway, we demonstrate that phosphatidylethanolamine is a direct precursor of the ethanolamine-phosphoglycerol moiety. Down-regulation of the expression of ethanolamine kinase and ethanolamine-phosphate cytidylyltransferase results in inhibition of phosphatidylethanolamine synthesis in T. brucei procyclic forms and, concomitantly, in a block in glycosylphosphatidylinositol attachment to procyclins and ethanolamine-phosphoglycerol modification of eukaryotic elongation factor 1A.

Formation and function of phosphatidylserine and phosphatidylethanolamine in mammalian cells

“…Although plants were also originally thought to make PS exclusively by a base-exchange reaction, a PS synthase that is encoded by a cDNA with 54% identity to the yeast PS synthase has been identified in wheat plants [60]. In the parasite Trypanosoma brucei PS is made entirely by a base-exchange reaction of PE with L-serine [61].…”

An essential bacterial-type cardiolipin synthase mediates cardiolipin formation in a eukaryote

“…Radioactive lipids were detected on dried TLC plates using a radioisotope detector (Berthold Technologies) and quantified using the Rita Control software provided by the manufacturer. For quantification of lipid phosphorus, individual spots were scraped from TLC plates and quantified as described previously (59). In each chromatographic separation, appropriate lipid standards were carried along.…”

Phosphatidylethanolamine Deficiency in Mammalian Mitochondria Impairs Oxidative Phosphorylation and Alters Mitochondrial Morphology

“…In addition, PE is a precursor of the ϳ30% of hepatic phosphatidylcholine made via PE N-methyltransferase (24). PE is also a precursor of anandamide (N-arachidonoylethanolamine) (25,26), the ethanolamine moiety of glycosylphosphatidylinositol anchors of many cell surface signaling proteins (27), and the ethanolamine linked to eukaryotic elongation factor eEF1A (28). Furthermore, PE appears to be required for autophagosome formation (12,29) and prion propagation in the brain (30).…”