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Pre- and post-Golgi translocation of glucosylceramide in glycosphingolipid synthesis
Glycosphingolipids are controlled by the spatial organization of their metabolism and by transport specificity. Using immunoelectron microscopy, we localize to the Golgi stack the glycosyltransferases that produce glucosylceramide (GlcCer), lactosylceramide (LacCer), and GM3. GlcCer is synthesized o...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064740/ https://www.ncbi.nlm.nih.gov/pubmed/17923531 http://dx.doi.org/10.1083/jcb.200704091 |
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author | Halter, David Neumann, Sylvia van Dijk, Suzanne M. Wolthoorn, Jasja de Mazière, Ann M. Vieira, Otilia V. Mattjus, Peter Klumperman, Judith van Meer, Gerrit Sprong, Hein |
author_facet | Halter, David Neumann, Sylvia van Dijk, Suzanne M. Wolthoorn, Jasja de Mazière, Ann M. Vieira, Otilia V. Mattjus, Peter Klumperman, Judith van Meer, Gerrit Sprong, Hein |
author_sort | Halter, David |
collection | PubMed |
description | Glycosphingolipids are controlled by the spatial organization of their metabolism and by transport specificity. Using immunoelectron microscopy, we localize to the Golgi stack the glycosyltransferases that produce glucosylceramide (GlcCer), lactosylceramide (LacCer), and GM3. GlcCer is synthesized on the cytosolic side and must translocate across to the Golgi lumen for LacCer synthesis. However, only very little natural GlcCer translocates across the Golgi in vitro. As GlcCer reaches the cell surface when Golgi vesicular trafficking is inhibited, it must translocate across a post-Golgi membrane. Concanamycin, a vacuolar proton pump inhibitor, blocks translocation independently of multidrug transporters that are known to translocate short-chain GlcCer. Concanamycin did not reduce LacCer and GM3 synthesis. Thus, GlcCer destined for glycolipid synthesis follows a different pathway and transports back into the endoplasmic reticulum (ER) via the late Golgi protein FAPP2. FAPP2 knockdown strongly reduces GM3 synthesis. Overall, we show that newly synthesized GlcCer enters two pathways: one toward the noncytosolic surface of a post-Golgi membrane and one via the ER toward the Golgi lumen LacCer synthase. |
format | Text |
id | pubmed-2064740 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-20647402008-04-08 Pre- and post-Golgi translocation of glucosylceramide in glycosphingolipid synthesis Halter, David Neumann, Sylvia van Dijk, Suzanne M. Wolthoorn, Jasja de Mazière, Ann M. Vieira, Otilia V. Mattjus, Peter Klumperman, Judith van Meer, Gerrit Sprong, Hein J Cell Biol Research Articles Glycosphingolipids are controlled by the spatial organization of their metabolism and by transport specificity. Using immunoelectron microscopy, we localize to the Golgi stack the glycosyltransferases that produce glucosylceramide (GlcCer), lactosylceramide (LacCer), and GM3. GlcCer is synthesized on the cytosolic side and must translocate across to the Golgi lumen for LacCer synthesis. However, only very little natural GlcCer translocates across the Golgi in vitro. As GlcCer reaches the cell surface when Golgi vesicular trafficking is inhibited, it must translocate across a post-Golgi membrane. Concanamycin, a vacuolar proton pump inhibitor, blocks translocation independently of multidrug transporters that are known to translocate short-chain GlcCer. Concanamycin did not reduce LacCer and GM3 synthesis. Thus, GlcCer destined for glycolipid synthesis follows a different pathway and transports back into the endoplasmic reticulum (ER) via the late Golgi protein FAPP2. FAPP2 knockdown strongly reduces GM3 synthesis. Overall, we show that newly synthesized GlcCer enters two pathways: one toward the noncytosolic surface of a post-Golgi membrane and one via the ER toward the Golgi lumen LacCer synthase. The Rockefeller University Press 2007-10-08 /pmc/articles/PMC2064740/ /pubmed/17923531 http://dx.doi.org/10.1083/jcb.200704091 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Halter, David Neumann, Sylvia van Dijk, Suzanne M. Wolthoorn, Jasja de Mazière, Ann M. Vieira, Otilia V. Mattjus, Peter Klumperman, Judith van Meer, Gerrit Sprong, Hein Pre- and post-Golgi translocation of glucosylceramide in glycosphingolipid synthesis |
title | Pre- and post-Golgi translocation of glucosylceramide in glycosphingolipid synthesis |
title_full | Pre- and post-Golgi translocation of glucosylceramide in glycosphingolipid synthesis |
title_fullStr | Pre- and post-Golgi translocation of glucosylceramide in glycosphingolipid synthesis |
title_full_unstemmed | Pre- and post-Golgi translocation of glucosylceramide in glycosphingolipid synthesis |
title_short | Pre- and post-Golgi translocation of glucosylceramide in glycosphingolipid synthesis |
title_sort | pre- and post-golgi translocation of glucosylceramide in glycosphingolipid synthesis |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064740/ https://www.ncbi.nlm.nih.gov/pubmed/17923531 http://dx.doi.org/10.1083/jcb.200704091 |
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