RRC ID 57203
Author Huang Y, Huang S, Di Scala C, Wang Q, Wandall HH, Fantini J, Zhang YQ.
Title The glycosphingolipid MacCer promotes synaptic bouton formation in Drosophila by interacting with Wnt.
Journal Elife
Abstract 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.
Volume 7
Published 2018-10-25
DOI 10.7554/eLife.38183
PII 38183
PMID 30355446
PMC PMC6202054
MeSH Animals Drosophila / physiology* Drosophila Proteins / metabolism* Glycosphingolipids / metabolism* Neuromuscular Junction / drug effects* Presynaptic Terminals / drug effects* Wnt Signaling Pathway / drug effects* Wnt1 Protein / metabolism*
IF 7.551
Times Cited 8