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

Yan Huang (1) , Sheng Huang (2) , Coralie Di Scala (3) , Qifu Wang , Hans H Wandall , Jacques Fantini (4) , Yong Zhang (5)

1 Mechanical and Electrical Engineering College [Hohhot]
2 SIAP - Shanghai Institute of Applied Physics
3 INMED - INSERM U1249 - Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université]
4 LVR - Laboratoire Vision et Robotique
5 China Huan-Qiu Contracting & Engineering Corporation (HQCEC)

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.

Mots clés: Lipids - Metabolism; Cellular membrane; Drosophila neuromuscular junction

Domaines: Neurosciences [q-bio.NC]; Neurobiologie

Yan Huang, Sheng Huang, Coralie Di Scala, Qifu Wang, Hans H Wandall, et al.. The glycosphingolipid MacCer promotes synaptic bouton formation in Drosophila by interacting with Wnt. eLife, 2018. ⟨hal-01963489⟩