The N-glycosylation defect of cwh8Δ yeast cells causes a distinct defect in sphingolipid biosynthesis
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Pittet, Martine
Department of Medicine, University of Fribourg, Switzerland
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Uldry, Danièle
Department of Medicine, University of Fribourg, Switzerland
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Aebi, Markus
Department of Biology, Institute of Microbiology, ETHZ, Zurich, Switzerland
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Conzelmann, Andreas
Department of Medicine, University of Fribourg, Switzerland
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Published in:
- Glycobiology. - 2006, vol. 16, no. 2, p. 155-164
English
CWH8/YGR036c of Saccharomyces cerevisiae has been identified as a dolichylpyrophosphate (Dol-PP) phosphatase that removes a phosphate from the Dol-PP generated by the oligosaccharyltransferase (OST), while it adds N-glycans to nascent glycoproteins in the endoplasmic reticulum (ER). Lack of CWH8 was proposed to interrupt the so called dolichol (Dol) cycle by trapping Dol in the form of Dol-PP in the ER lumen. Indeed, cwh8D mutants display a severe deficiency in N-glycosylation. We find that cwh8D mutants have strongly reduced levels of inositolphosphorylceramide (IPC), whereas its derivative, mannosyl-(inositol-P)₂-ceramide (M(IP)₂C) is not affected. Microsomes of cwh8D contain normal ceramide synthase and IPC synthesis activities. Within a large panel of mutants affecting Dol dependent pathways such as N- or O-glycosylation, or glycosylphosphatidyl inositol (GPI)-anchoring, only the mutants having a deficiency of N-glycan addition show the defect in IPC biosynthesis. By mutating genes required for the addition of N-glycans or by treating cells with tunicamycin (Tm) one can similarly reduce the steady state level of IPC and exactly reproduce the phenotype of cwh8D cells. Some potential mechanisms by which the lack of N-glycans could lead to the sphingolipid abnormality were further explored.
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Faculty
- Faculté des sciences et de médecine
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Department
- Département de Biologie
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Language
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Classification
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Biological sciences
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License
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License undefined
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Identifiers
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Persistent URL
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https://folia.unifr.ch/unifr/documents/300100
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