<i>Saccharomyces cerevisiae CWH43</i>Is Involved in the Remodeling of the Lipid Moiety of GPI Anchors to Ceramides

Umemura, Masayuki; Fujita, Morihisa; Yoko-o, Takehiko; Fukamizu, Akiyoshi; Jigami, Yoshifumi

doi:10.1091/mbc.e07-05-0482

Cited by 68 publications

(89 citation statements)

References 53 publications

(79 reference statements)

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“…Many GPIs are next remodeled by replacement of their diacylglycerol with ceramide by Cwh43 Ghugtyal et al 2007;Umemura et al 2007). Ceramide remodeling requires prior action of Bst1, and, because per1D and gup1D strains show defects in remodeling, the exchange reaction likely takes place after the first three lipid modification steps.…”

Section: Gpi Anchoringmentioning

confidence: 99%

“…Cwh43, which replaces the diacylglycerol moiety of GPIs with ceramide, is a large protein with 19 predicted transmembrane domains Ghugtyal et al 2007;Umemura et al 2007). cwh43Δ cells accumulate GPI--proteins whose lipids are diacylglycerols with a very long acyl chain similar to the lipid generated after action of Bst1, Per1, and Gup1.…”

Section: Remodeling Of Protein--bound Gpismentioning

confidence: 99%

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Architecture and Biosynthesis of the Saccharomyces cerevisiae Cell Wall

2012

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The wall gives a Saccharomyces cerevisiae cell its osmotic integrity; defines cell shape during budding growth, mating, sporulation, and pseudohypha formation; and presents adhesive glycoproteins to other yeast cells. The wall consists of b1,3-and b1,6-glucans, a small amount of chitin, and many different proteins that may bear N-and O-linked glycans and a glycolipid anchor. These components become cross-linked in various ways to form higher-order complexes. Wall composition and degree of cross-linking vary during growth and development and change in response to cell wall stress. This article reviews wall biogenesis in vegetative cells, covering the structure of wall components and how they are cross-linked; the biosynthesis of N-and O-linked glycans, glycosylphosphatidylinositol membrane anchors, b1,3-and b1,6-linked glucans, and chitin; the reactions that cross-link wall components; and the possible functions of enzymatic and nonenzymatic cell wall proteins. TABLE OF CONTENTS Abstract 775Introduction 777

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Section: Gpi Anchoringmentioning

confidence: 99%

Section: Remodeling Of Protein--bound Gpismentioning

confidence: 99%

Architecture and Biosynthesis of the Saccharomyces cerevisiae Cell Wall

2012

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“…Cwh43⌬ and other mutants, which do not incorporate ceramides into GPI anchors, are viable (33)(34)(35), indicating that ceramide is not an essential component of GPI anchors. The incorporation of ceramides into GPI anchors supposedly is analogous to the IPC synthase reaction carried out by Aur1p, but it seems to be independent of Aur1p because it cannot be inhibited by AbA (36).…”

Section: Slc1-1 Significantly Increases the Fitness Of Lag1⌬ Lac1⌬mentioning

confidence: 99%

Yeast Cells Lacking All Known Ceramide Synthases Continue to Make Complex Sphingolipids and to Incorporate Ceramides into Glycosylphosphatidylinositol (GPI) Anchors

Vionnet

Roubaty

Ejsing

et al. 2011

Journal of Biological Chemistry

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In yeast, the inositolphosphorylceramides mostly contain C26:0 fatty acids. Inositolphosphorylceramides were considered to be important for viability because the inositolphosphorylceramide synthase AUR1 is essential. However, lcb1⌬ cells, unable to make sphingoid bases and inositolphosphorylceramides, are viable if they harbor SLC1-1, a gain of function mutation in the 1-acyl-glycerol-3-phosphate acyltransferase SLC1. SLC1-1 allows the incorporation of C26:0 fatty acids into phosphatidylinositol (PI), thus generating PI؆, an abnormal, C26-containing PI, presumably acting as surrogate for inositolphosphorylceramide. Here we show that the lethality of the simultaneous deletion of the known ceramide synthases LAG1/LAC1/LIP1 and YPC1/YDC1 can be rescued by the expression of SLC1-1 or the overexpression of AUR1. Moreover, lag1⌬ lac1⌬ ypc1⌬ ydc1⌬ (4⌬) quadruple mutants have been reported to be viable in certain genetic backgrounds but to still make some abnormal uncharacterized inositol-containing sphingolipids. Indeed, we find that 4⌬ quadruple mutants make substantial amounts of unphysiological inositolphosphorylphytosphingosines but that they also still make small amounts of normal inositolphosphorylceramides. Moreover, 4⌬ strains incorporate exogenously added sphingoid bases into inositolphosphorylceramides, indicating that these cells still possess an unknown pathway allowing the synthesis of ceramides. 4⌬ cells also still add quite normal amounts of ceramides to glycosylphosphatidylinositol anchors. Synthesis of inositolphosphorylceramides and inositolphosphorylphytosphingosines is operated by Aur1p and is essential for growth of all 4⌬ cells unless they contain SLC1-1. PI؆, however, is made without the help of Aur1p. Furthermore, mannosylation of PI؆ is required for the survival of sphingolipid-deficient strains, which depend on SLC1-1. In contrast to lcb1⌬ SLC1-1, 4⌬ SLC1-1 cells grow at 37°C but remain thermosensitive at 44°C.

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“…Cwh43p is involved in the ceramide remodeling of GPI-anchors (61,62). The N-terminal region of Cwh43p is homologous to mammalian PGAP2 and the C-terminal region contains a motif observed in inositolphosphoceramide phospholipase C and sphingomyelinase.…”

Section: C-5 Other Remodeling Reactionsmentioning

confidence: 99%

“…Structural analysis revealed that the ceramide types of GPI-anchors are found in several organisms, including Aspergillus, American trypanosome, Dictyostelium, and plants (5). The existence of ceramide-containing GPI-anchored proteins in mammalian cells has not been reported; however, a protein homologous to the yeast C-terminal region of Cwh43p is known (62). Because the mammalian homolog of the C-terminal region of Cwh43 appears to be functional, at least in yeast, detailed analysis of the Cwh43p homolog in mammals, including its expression profile, is required.…”

Section: C-5 Other Remodeling Reactionsmentioning

confidence: 99%

Potential Roles of GPI-Anchor Remodeling in Protein Trafficking and Raft Association in Mammalian Cells

Fujita

2012

TIGG

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Post-translational modification of proteins with glycosylphosphatidylinositol (GPI) is mediated by a mechanism that is conserved in all eukaryotes. GPI-anchored proteins are characterized by their association with specialized membrane domains called "lipid rafts," and the GPI-anchors are thought to regulate their intracellular trafficking pathways. These characteristics are regulated by the structural properties of GPI-anchors, remodeling enzymes and recognition molecules. The biogenesis of GPI-anchored proteins occurs in the ER, following which they are transported to the plasma membrane via the Golgi apparatus. During transport, the structures of the GPI-anchors are remodeled. In this minireview, the structural remodeling of mammalian GPIanchors and regulation of the transport and localization of GPI-anchored proteins are described.

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Saccharomyces cerevisiae CWH43Is Involved in the Remodeling of the Lipid Moiety of GPI Anchors to Ceramides

Cited by 68 publications

References 53 publications

Architecture and Biosynthesis of the Saccharomyces cerevisiae Cell Wall

Architecture and Biosynthesis of the Saccharomyces cerevisiae Cell Wall

Yeast Cells Lacking All Known Ceramide Synthases Continue to Make Complex Sphingolipids and to Incorporate Ceramides into Glycosylphosphatidylinositol (GPI) Anchors

Potential Roles of GPI-Anchor Remodeling in Protein Trafficking and Raft Association in Mammalian Cells

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