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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.<\/jats:p>","DOI":"10.7554\/elife.38183","type":"journal-article","created":{"date-parts":[[2018,10,25]],"date-time":"2018-10-25T06:04:28Z","timestamp":1540447468000},"source":"Crossref","is-referenced-by-count":28,"title":["The glycosphingolipid MacCer promotes synaptic bouton formation in Drosophila by interacting with Wnt"],"prefix":"10.7554","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3833-9248","authenticated-orcid":true,"given":"Yan","family":"Huang","sequence":"first","affiliation":[{"name":"Key Laboratory for Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Key Laboratory for Molecular and 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