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

eLife

Coralie Di Scala¹  Jacques Fantini²  Qifu Wang³  Yan Huang⁴  Sheng Huang⁴  Hans H Wandall⁴  Yong Q Zhang⁵ 

[1] Sino-Danish College, Sino-Danish Center for Education and Research, Chinese Academy of Sciences, Beijing, China;Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark;INMED U1249, INSERM, Marseille, France;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;UNIS UMR_S 1072, INSERM, Aix-Marseille Université, Marseille, France;

关键词: Glycosphingolipid;    synaptic growth;    Wnt signaling;    lipid-protein interaction;   

DOI  :  10.7554/eLife.38183

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown