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

TY - JOUR

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 - 2018/10

Y1 - 2018/10

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

SN - 2050-084X

VL - 7

JO - eLife

JF - eLife

M1 - e38183

ER -