The glycosphingolipid MacCer promotes synaptic bouton formation in Drosophila by interacting with Wnt
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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.
I: eLife, Bind 7, e38183, 2018.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - The glycosphingolipid MacCer promotes synaptic bouton formation in Drosophila by interacting with Wnt
AU - Huang, Yan
AU - Huang, Sheng
AU - Di Scala, Coralie
AU - Wang, Qifu
AU - Wandall, Hans H.
AU - Fantini, Jacques
AU - Zhang, Yong Q.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - D. melanogaster
KW - developmental biology
KW - Glycosphingolipid
KW - lipid-protein interaction
KW - synaptic growth
KW - Wnt signaling
U2 - 10.7554/eLife.38183
DO - 10.7554/eLife.38183
M3 - Journal article
C2 - 30355446
AN - SCOPUS:85055605718
VL - 7
JO - eLife
JF - eLife
SN - 2050-084X
M1 - e38183
ER -
ID: 209546676