TY - JOUR TI - 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 A2 - VijayRaghavan, K A2 - Lloyd, Thomas VL - 7 PY - 2018 DA - 2018/10/25 SP - e38183 C1 - eLife 2018;7:e38183 DO - 10.7554/eLife.38183 UR - https://doi.org/10.7554/eLife.38183 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 - Glycosphingolipid KW - synaptic growth KW - Wnt signaling KW - lipid-protein interaction JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -