Faculté des sciences

Ethanolaminephosphate Side Chain Added to Glycosylphosphatidylinositol (GPI) Anchor by Mcd4p Is Required for Ceramide Remodeling and Forward Transport of GPI Proteins from Endoplasmic Reticulum to Golgi

Zhu, Yonghua ; Vionnet, Christine ; Conzelmann, Andreas

In: Journal of Biological Chemistry, 2006, vol. 281, no. 29, p. 19830-19839

Glycosylphosphatidylinositol (GPI) anchors of mammals as well as yeast contain ethanolaminephosphate side chains on the α1–4- and the α1–6-linked mannoses of the anchor core structure (protein-CO-NH-(CH₂)₂-PO₄-6Manα1–2Manα1–6Manα1–4GlcNH₂-inositol-PO₄-lipid). In yeast, the ethanolaminephosphate on the α1–4-linked mannose is added during the biosynthesis of the GPI... Plus

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    Summary
    Glycosylphosphatidylinositol (GPI) anchors of mammals as well as yeast contain ethanolaminephosphate side chains on the α1–4- and the α1–6-linked mannoses of the anchor core structure (protein-CO-NH-(CH₂)₂-PO₄-6Manα1–2Manα1–6Manα1–4GlcNH₂-inositol-PO₄-lipid). In yeast, the ethanolaminephosphate on the α1–4-linked mannose is added during the biosynthesis of the GPI lipid by Mcd4p. MCD4 is essential because Gpi10p, the mannosyltransferase adding the subsequent α1–2-linked mannose, requires substrates with an ethanolaminephosphate on the α1–4-linked mannose. The Gpi10p ortholog of Trypanosoma brucei has no such requirement. Here we show that the overexpression of this ortholog rescues mcd4δ cells. Phenotypic analysis of the rescued mcd4δ cells leads to the conclusion that the ethanolaminephosphate on the α1–4-linked mannose, beyond being an essential determinant for Gpi10p, is necessary for an efficient recognition of GPI lipids and GPI proteins by the GPI transamidase for the efficient transport of GPI-anchored proteins from the endoplasmic reticulum to Golgi and for the physiological incorporation of ceramides into GPI anchors by lipid remodeling. Furthermore, mcd4δ cells have a marked defect in axial bud site selection, whereas this process is normal in gpi7δ and gpi1. This also suggests that axial bud site selection specifically depends on the presence of the ethanolaminephosphate on the α1–4-linked mannose