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The glycosphingolipid MacCer promotes synaptic bouton formation in Drosophila by interacting with Wnt

Lipids are structural components of cellular membranes and signaling molecules that are widely involved in development and diseases, but the underlying molecular mechanisms are poorly understood, partly because of the vast variety of lipid species and complexity of synthetic and turnover pathways. F...

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Autores principales: Huang, Yan, Huang, Sheng, Di Scala, Coralie, Wang, Qifu, Wandall, Hans H, Fantini, Jacques, Zhang, Yong Q
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202054/
https://www.ncbi.nlm.nih.gov/pubmed/30355446
http://dx.doi.org/10.7554/eLife.38183
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author Huang, Yan
Huang, Sheng
Di Scala, Coralie
Wang, Qifu
Wandall, Hans H
Fantini, Jacques
Zhang, Yong Q
author_facet Huang, Yan
Huang, Sheng
Di Scala, Coralie
Wang, Qifu
Wandall, Hans H
Fantini, Jacques
Zhang, Yong Q
author_sort Huang, Yan
collection PubMed
description Lipids are structural components of cellular membranes and signaling molecules that are widely involved in development and diseases, but the underlying molecular mechanisms are poorly understood, partly because of the vast variety of lipid species and complexity of synthetic and turnover pathways. From a genetic screen, we identify that mannosyl glucosylceramide (MacCer), a species of glycosphingolipid (GSL), promotes synaptic bouton formation at the Drosophila neuromuscular junction (NMJ). Pharmacological and genetic analysis shows that the NMJ growth-promoting effect of MacCer depends on normal lipid rafts, which are known to be composed of sphingolipids, sterols and select proteins. MacCer positively regulates the synaptic level of Wnt1/Wingless (Wg) and facilitates presynaptic Wg signaling, whose activity is raft-dependent. Furthermore, a functional GSL-binding motif in Wg exhibiting a high affinity for MacCer is required for normal NMJ growth. These findings reveal a novel mechanism whereby the GSL MacCer promotes synaptic bouton formation via Wg signaling.
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spelling pubmed-62020542018-11-05 The glycosphingolipid MacCer promotes synaptic bouton formation in Drosophila by interacting with Wnt Huang, Yan Huang, Sheng Di Scala, Coralie Wang, Qifu Wandall, Hans H Fantini, Jacques Zhang, Yong Q eLife Developmental Biology Lipids are structural components of cellular membranes and signaling molecules that are widely involved in development and diseases, but the underlying molecular mechanisms are poorly understood, partly because of the vast variety of lipid species and complexity of synthetic and turnover pathways. From a genetic screen, we identify that mannosyl glucosylceramide (MacCer), a species of glycosphingolipid (GSL), promotes synaptic bouton formation at the Drosophila neuromuscular junction (NMJ). Pharmacological and genetic analysis shows that the NMJ growth-promoting effect of MacCer depends on normal lipid rafts, which are known to be composed of sphingolipids, sterols and select proteins. MacCer positively regulates the synaptic level of Wnt1/Wingless (Wg) and facilitates presynaptic Wg signaling, whose activity is raft-dependent. Furthermore, a functional GSL-binding motif in Wg exhibiting a high affinity for MacCer is required for normal NMJ growth. These findings reveal a novel mechanism whereby the GSL MacCer promotes synaptic bouton formation via Wg signaling. eLife Sciences Publications, Ltd 2018-10-25 /pmc/articles/PMC6202054/ /pubmed/30355446 http://dx.doi.org/10.7554/eLife.38183 Text en © 2018, Huang et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Developmental Biology
Huang, Yan
Huang, Sheng
Di Scala, Coralie
Wang, Qifu
Wandall, Hans H
Fantini, Jacques
Zhang, Yong Q
The glycosphingolipid MacCer promotes synaptic bouton formation in Drosophila by interacting with Wnt
title The glycosphingolipid MacCer promotes synaptic bouton formation in Drosophila by interacting with Wnt
title_full The glycosphingolipid MacCer promotes synaptic bouton formation in Drosophila by interacting with Wnt
title_fullStr The glycosphingolipid MacCer promotes synaptic bouton formation in Drosophila by interacting with Wnt
title_full_unstemmed The glycosphingolipid MacCer promotes synaptic bouton formation in Drosophila by interacting with Wnt
title_short The glycosphingolipid MacCer promotes synaptic bouton formation in Drosophila by interacting with Wnt
title_sort glycosphingolipid maccer promotes synaptic bouton formation in drosophila by interacting with wnt
topic Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202054/
https://www.ncbi.nlm.nih.gov/pubmed/30355446
http://dx.doi.org/10.7554/eLife.38183
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