Identification of SPT14/CWH6 as the yeast homologue of hPIG-A, a gene involved in the biosynthesis of GPI anchors

Vossen, Jack H.; Ram, Arthur F. J.; Klis, Frans M.

doi:10.1016/0304-4165(95)00002-s

Cited by 51 publications

(45 citation statements)

References 15 publications

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“…The GlcNAc transfer reaction is unexpectedly complex in that many proteins are involved. The mammalian proteins and their yeast orthologs are PIG-A/Gpi3p, PIG-C/Gpi2p, PIG-H/Gpi15p, PIG-P/Gpi19p, PIG-Q(hGpi1p)/Gpi1p, and PIG-Y/Eri1p (50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65). In mammalian cells, a seventh protein, Dpm2p, a noncatalytic subunit of Dol-P-Man synthase, physically associates with the PIG-A, -C, and -Q proteins and enhances GlcNAc-PI synthetic activity (58).…”

Section: Biosynthesis Of the Gpi Precursormentioning

confidence: 99%

Thematic review series: Lipid Posttranslational Modifications. GPI anchoring of protein in yeast and mammalian cells, or: how we learned to stop worrying and love glycophospholipids

Orlean

Menon

2007

Journal of Lipid Research

361

293

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Glycosylphosphatidylinositol (GPI) anchoring of cell surface proteins is the most complex and metabolically expensive of the lipid posttranslational modifications described to date. The GPI anchor is synthesized via a membrane-bound multistep pathway in the endoplasmic reticulum (ER) requiring .20 gene products. The pathway is initiated on the cytoplasmic side of the ER and completed in the ER lumen, necessitating flipping of a glycolipid intermediate across the membrane. The completed GPI anchor is attached to proteins that have been translocated across the ER membrane and that display a GPI signal anchor sequence at the C terminus. GPI proteins transit the secretory pathway to the cell surface; in yeast, many become covalently attached to the cell wall. Genes encoding proteins involved in all but one of the predicted steps in the assembly of the GPI precursor glycolipid and its transfer to protein in mammals and yeast have now been identified. Most of these genes encode polytopic membrane proteins, some of which are organized in complexes. The steps in GPI assembly, and the enzymes that carry them out, are highly conserved. GPI biosynthesis is essential for viability in yeast and for embryonic development in mammals. In this review, we describe the biosynthesis of mammalian and yeast GPIs, their transfer to protein, and their subsequent processing.-Orlean, P., and A. K. Menon. GPI anchoring of protein in yeast and mammalian cells, or: how we learned to stop worrying and love glycophospholipids.

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Section: Biosynthesis Of the Gpi Precursormentioning

confidence: 99%

Thematic review series: Lipid Posttranslational Modifications. GPI anchoring of protein in yeast and mammalian cells, or: how we learned to stop worrying and love glycophospholipids

Orlean

Menon

2007

Journal of Lipid Research

361

293

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“…This step is catalysed in humans by a complex of seven proteins: PIG-A, PIG-P, PIG-C, PIG-H, PIG-Q, PIG-Y and DPM2 (Watanabe et al, 1996(Watanabe et al, , 1998(Watanabe et al, , 2000Murakami et al, 2005), collectively referred to as the GPIGnT complex. Homologues of all proteins, except DPM2, have also been identified in members of the genus Saccharomyces (Vossen et al, 1995;Leidich et al, 1995;Leidich & Orlean, 1996;Yan et al, 2001). In C. albicans, very few studies have been carried out on the GPI anchor biosynthetic pathway itself and these have been restricted to genes further downstream in the pathway, for example CaSMP3 and Candida GPI7/LAS2 (Grimme et al, 2004;Richard et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

The Candida albicans homologue of PIG-P, CaGpi19p: gene dosage and role in growth and filamentation

2010

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Glycosylphosphatidyl inositol (GPI)-anchored proteins in Candida albicans are responsible for a vast range of functions, and deletions in certain GPI-anchored proteins severely reduce adhesion and virulence of this organism. In addition, completely modified GPIs are necessary for virulence. GPI anchor biosynthesis is essential for viability and starts with the transfer of N-acetylglucosamine to phosphatidylinositol. This step is catalysed by a multi-subunit complex, GPI–N-acetylglucosaminyltransferase (GPI–GnT). In this, the first report to our knowledge on a subunit of the Candida GPI–GnT complex, we show that CaGpi19p is the functional equivalent of the Saccharomyces cerevisiae Gpi19p. An N-terminal truncation mutant of CaGpi19p functionally complements a conditionally lethal S. cerevisiae gpi19 mutant. Further, we constructed a conditional null mutant of CaGPI19 by disrupting one allele and placing the remaining copy under the control of the MET3 promoter. Repression leads to growth defects, cell wall biogenesis aberrations, azole sensitivity and hyperfilamention. In addition, there is a noticeable gene dosage effect, with the heterozygote also displaying intermediate degrees of most phenotypes. The mutants also displayed a reduced susceptibility to the antifungal agent amphotericin B. Collectively, the results suggest that CaGPI19 is required for normal morphology and cell wall architecture.

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“…Analysis of mutants hypersensitive to calcofluor white has resulted in the identification of numerous genes involved in different aspects of cell wall biogenesis Jiang et al, 1995Jiang et al, , 1996Vossen et al, 1995 ;Van Berkel et al, 1999). In addition, screening for mutants resistant to this…”

Section: Introductionmentioning

confidence: 99%

The protein kinase Kic1 affects 1,6-β-glucan levels in the cell wall of Saccharomyces cerevisiae

Vink¹,

Vossen²,

Ende³

et al. 2002

Microbiology

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KIC1 encodes a PAK kinase that is involved in morphogenesis and cell integrity. Both over-and underexpressing conditions of KIC1 affected cell wall composition. Kic1-deficient cells were hypersensitive to the cell wall perturbing agent calcofluor white and had less 1,6-β-glucan. When Kic1-deficient cells were crossed with various kre mutants, which also have less 1,6-β-glucan in their wall, the double mutants displayed synthetic growth defects.However, when crossed with the 1,3-β-glucan-deficient strain fks1∆, no synthetic growth defect was observed, supporting a specific role for KIC1 in regulating 1,6-β-glucan levels. Kic1-deficient cells also became highly resistant to the cell wall-degrading enzyme mixture Zymolyase, and exhibited higher transcript levels of the cell wall protein-encoding genes CWP2 and SED1. Conversely, overexpression of KIC1 resulted in increased sensitivity to Zymolyase and in a higher level of 1,6-β-glucan. Multicopy suppressor analysis of a Kic1-deficient strain identified RHO3. Consistent with this, expression levels of RHO3 correlated with 1,6-β-glucan levels in the cell wall. Interestingly, expression levels of KIC1 and the MAP kinase kinase PBS2 had opposite effects on Zymolyase sensitivity of the cells and on cell wall 1,6-β-glucan levels in the wall. It is proposed that Kic1 affects cell wall construction in multiple ways and in particular in regulating 1,6-β-glucan levels in the wall.

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Identification of SPT14/CWH6 as the yeast homologue of hPIG-A, a gene involved in the biosynthesis of GPI anchors

Cited by 51 publications

References 15 publications

Thematic review series: Lipid Posttranslational Modifications. GPI anchoring of protein in yeast and mammalian cells, or: how we learned to stop worrying and love glycophospholipids

Thematic review series: Lipid Posttranslational Modifications. GPI anchoring of protein in yeast and mammalian cells, or: how we learned to stop worrying and love glycophospholipids

The Candida albicans homologue of PIG-P, CaGpi19p: gene dosage and role in growth and filamentation

The protein kinase Kic1 affects 1,6-β-glucan levels in the cell wall of Saccharomyces cerevisiae

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