Biosynthesis and function of GPI proteins in the yeast Saccharomyces cerevisiae

Abstract

Like most other eukaryotes, Saccharomyces cerevisiae harbors a GPI anchoring machinery and uses it to attach proteins to membranes. While a few GPI proteins reside permanently at the plasma membrane, a majority of them gets further processed and is integrated into the cell wall by a covalent attachment to cell wall glucans. The GPI biosynthetic pathway is necessary for growth and survival of yeast cells. The GPI lipids are synthesized in the ER and added onto proteins by a pathway comprising 12 steps, carried out by 23 gene products, 19 of which are essential. Some of the estimated 60 GPI proteins predicted from the genome sequence serve enzymatic functions required for the biosynthesis and the continuous shape adaptations of the cell wall, others seem to be structural elements of the cell wall and yet others mediate cell adhesion. Because of its genetic tractability S. cerevisiae is an attractive model organism not only for studying GPI biosynthesis in general, but equally for investigating the intracellular transport of GPI proteins and the peculiar role of GPI anchoring in the elaboration of fungal cell walls.

Secretory Protein Biogenesis and Traffic in the Early Secretory Pathway

“…The synthesis and attachment of GPI anchors occur in the ER through a multistep pathway that depends on .20 gene products (Orlean and Menon 2007). GPI synthesis and attachment are essential processes in yeast and GPI anchored proteins on the cell surface are thought to play critical roles in cell wall structure and cell morphology (Leidich et al 1994;Pittet and Conzelmann 2007). As with assembly of the N-linked core oligosaccharide, the GPI anchor is fully synthesized as a lipid anchored precursor and then transferred to target proteins en bloc by the GPI transamidase complex (Fraering et al 2001).…”

myo-Inositol Uptake Is Essential for Bulk Inositol Phospholipid but Not Glycosylphosphatidylinositol Synthesis in Trypanosoma brucei

“…In contrast, myo-[ 3 H]inositol is the preferred substrate to label GPI anchors in S. cerevisiae (reviewed in Ref. 65), suggesting that yeast may be able to transport myoinositol into the ER or that the active site of yeast PI synthase faces the cytosol.…”

Pga1 Is an Essential Component of Glycosylphosphatidylinositol-Mannosyltransferase II ofSaccharomyces cerevisiae

“…As shown in Figure 11, several steps in GPI biosynthesis are reported to be carried out by the participation of multiple proteins (Kinoshita and Inoue, 2000;Pittet and Conzelmann, 2006). Both mammalian and budding yeast GPI-MT I are a complex of a multimembrane-spanning protein (PIG-M/Gpi14) and a single membrane-spanning protein (PIG-X/Pbn1).…”

“…The GPI is a complex glycolipid with a core structure, phosphoethanolamine (EtN-P)-6-mannose (Man)-␣1,2-Man-␣1,6-Man-␣1,4-glucosamine (GlcN)-␣1,6-inositol-phospholipid, that is conserved in all eukaryotic cells (Kinoshita and Inoue, 2000) and functions as a membrane anchor for many cell surface proteins (Englund, 1993). In budding yeast Saccharomyces cerevisiae, GPI synthesis and GPI-anchoring are carried out by Ͼ20 gene products, and most of the genes are essential for cell viability (Pittet and Conzelmann, 2006). Many GPI-anchored proteins lose lipid moiety at a certain stage of maturation, and they become attached to the cell wall ␤1,6-glucan through the remaining mannose residues, contributing to the cell wall integrity (Lu et al, 1995).…”