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

Research output: Contribution to journalJournal articlepeer-review

  • Yan Huang
  • Sheng Huang
  • Coralie Di Scala
  • Qifu Wang
  • Wandall, Hans H.
  • Jacques Fantini
  • Yong Q. Zhang

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.

Original languageEnglish
Article numbere38183
JournaleLife
Volume7
Number of pages29
ISSN2050-084X
DOIs
Publication statusPublished - 2018

    Research areas

  • D. melanogaster, developmental biology, Glycosphingolipid, lipid-protein interaction, synaptic growth, Wnt signaling

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