Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Journal of Biological Chemistry |
| Vol/bind | 280 |
| Udgave nummer | 6 |
| Sider (fra-til) | 4858-63 |
| Antal sider | 5 |
| ISSN | 0021-9258 |
| DOI | |
| Status | Udgivet - 2004 |
Bibliografisk note
Keywords: Alleles; Animals; Antibodies, Monoclonal; CHO Cells; Ceramides; Chromatography, High Pressure Liquid; Cricetinae; Drosophila Proteins; Drosophila melanogaster; Gene Expression Regulation; Glycosphingolipids; Golgi Apparatus; Humans; Magnetic Resonance Spectroscopy; Membrane Proteins; Models, Biological; Models, Genetic; Mutation; Protein ConformationAdgang til dokumentet
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I: Journal of Biological Chemistry, Bind 280, Nr. 6, 2004, s. 4858-63.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - Egghead and brainiac are essential for glycosphingolipid biosynthesis in vivo.
AU - Wandall, Hans H
AU - Pizette, Sandrine
AU - Pedersen, Johannes W
AU - Eichert, Heather
AU - Levery, Steven B
AU - Mandel, Ulla
AU - Cohen, Stephen M
AU - Clausen, Henrik
N1 - Keywords: Alleles; Animals; Antibodies, Monoclonal; CHO Cells; Ceramides; Chromatography, High Pressure Liquid; Cricetinae; Drosophila Proteins; Drosophila melanogaster; Gene Expression Regulation; Glycosphingolipids; Golgi Apparatus; Humans; Magnetic Resonance Spectroscopy; Membrane Proteins; Models, Biological; Models, Genetic; Mutation; Protein Conformation
PY - 2004
Y1 - 2004
N2 - The Drosophila genes, brainiac and egghead, encode glycosyltransferases predicted to act sequentially in early steps of glycosphingolipid biosynthesis, and both genes are required for development in Drosophila. egghead encodes a beta4-mannosyltransferase, and brainiac encodes a beta3-N-acetylglucosaminyltransferase predicted by in vitro analysis to control synthesis of the glycosphingolipid core structure, GlcNAcbeta1-3Manbeta1-4Glcbeta1-Cer, found widely in invertebrates but not vertebrates. In this report we present direct in vivo evidence for this hypothesis. egghead and brainiac mutants lack elongated glycosphingolipids and exhibit accumulation of the truncated precursor glycosphingolipids. Furthermore, we demonstrate that despite fundamental differences in the core structure of mammalian and Drosophila glycosphingolipids, the Drosophila egghead mutant can be rescued by introduction of the mammalian lactosylceramide glycosphingolipid biosynthetic pathway (Galbeta1-4Glcbeta1-Cer) using a human beta4-galactosyltransferase (beta4Gal-T6) transgene. Conversely, introduction of egghead in vertebrate cells (Chinese hamster ovary) resulted in near complete blockage of biosynthesis of glycosphingolipids and accumulation of Manbeta1-4Glcbeta1-Cer. The study demonstrates that glycosphingolipids are essential for development of complex organisms and suggests that the function of the Drosophila glycosphingolipids in development does not depend on the core structure.
AB - The Drosophila genes, brainiac and egghead, encode glycosyltransferases predicted to act sequentially in early steps of glycosphingolipid biosynthesis, and both genes are required for development in Drosophila. egghead encodes a beta4-mannosyltransferase, and brainiac encodes a beta3-N-acetylglucosaminyltransferase predicted by in vitro analysis to control synthesis of the glycosphingolipid core structure, GlcNAcbeta1-3Manbeta1-4Glcbeta1-Cer, found widely in invertebrates but not vertebrates. In this report we present direct in vivo evidence for this hypothesis. egghead and brainiac mutants lack elongated glycosphingolipids and exhibit accumulation of the truncated precursor glycosphingolipids. Furthermore, we demonstrate that despite fundamental differences in the core structure of mammalian and Drosophila glycosphingolipids, the Drosophila egghead mutant can be rescued by introduction of the mammalian lactosylceramide glycosphingolipid biosynthetic pathway (Galbeta1-4Glcbeta1-Cer) using a human beta4-galactosyltransferase (beta4Gal-T6) transgene. Conversely, introduction of egghead in vertebrate cells (Chinese hamster ovary) resulted in near complete blockage of biosynthesis of glycosphingolipids and accumulation of Manbeta1-4Glcbeta1-Cer. The study demonstrates that glycosphingolipids are essential for development of complex organisms and suggests that the function of the Drosophila glycosphingolipids in development does not depend on the core structure.
U2 - 10.1074/jbc.C400571200
DO - 10.1074/jbc.C400571200
M3 - Journal article
C2 - 15611100
SN - 0021-9258
VL - 280
SP - 4858
EP - 4863
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 6
ER -