» Articles » PMID: 30355446

The Glycosphingolipid MacCer Promotes Synaptic Bouton Formation in Drosophila by Interacting with Wnt

Overview
Journal Elife
Specialty Biology
Date 2018 Oct 26
PMID 30355446
Citations 9
Authors
Affiliations
Soon will be listed here.
Abstract

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 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.

Citing Articles

Glycosphingolipids are linked to elevated neurotransmission and neurodegeneration in a Drosophila model of Niemann Pick type C.

Eberwein A, Kulkarni S, Rushton E, Broadie K Dis Model Mech. 2023; 16(10).

PMID: 37815467 PMC: 10581387. DOI: 10.1242/dmm.050206.


Gbb glutathionylation promotes its proteasome-mediated degradation to inhibit synapse growth.

Hossain M, Yao A, Qiao X, Shi W, Xie T, Chen C J Cell Biol. 2023; 222(9).

PMID: 37389657 PMC: 10316630. DOI: 10.1083/jcb.202202068.


Drosophila motor neuron boutons remodel through membrane blebbing coupled with muscle contraction.

Fernandes A, Martins J, Gomes E, Mendes C, Teodoro R Nat Commun. 2023; 14(1):3352.

PMID: 37291089 PMC: 10250368. DOI: 10.1038/s41467-023-38421-9.


Glial control of sphingolipid levels sculpts diurnal remodeling in a circadian circuit.

Vaughen J, Theisen E, Rivas-Serna I, Berger A, Kalakuntla P, Anreiter I Neuron. 2022; 110(19):3186-3205.e7.

PMID: 35961319 PMC: 10868424. DOI: 10.1016/j.neuron.2022.07.016.


Regulation of Wnt Signaling Pathways at the Plasma Membrane and Their Misregulation in Cancer.

Azbazdar Y, Karabicici M, Erdal E, Ozhan G Front Cell Dev Biol. 2021; 9:631623.

PMID: 33585487 PMC: 7873896. DOI: 10.3389/fcell.2021.631623.


References
1.
Yu R, Nakatani Y, Yanagisawa M . The role of glycosphingolipid metabolism in the developing brain. J Lipid Res. 2008; 50 Suppl:S440-5. PMC: 2674698. DOI: 10.1194/jlr.R800028-JLR200. View

2.
Vacaru A, van den Dikkenberg J, Ternes P, Holthuis J . Ceramide phosphoethanolamine biosynthesis in Drosophila is mediated by a unique ethanolamine phosphotransferase in the Golgi lumen. J Biol Chem. 2013; 288(16):11520-30. PMC: 3630839. DOI: 10.1074/jbc.M113.460972. View

3.
Miech C, Pauer H, He X, Schwarz T . Presynaptic local signaling by a canonical wingless pathway regulates development of the Drosophila neuromuscular junction. J Neurosci. 2008; 28(43):10875-84. PMC: 2597682. DOI: 10.1523/JNEUROSCI.0164-08.2008. View

4.
Resh M . Membrane targeting of lipid modified signal transduction proteins. Subcell Biochem. 2004; 37:217-32. DOI: 10.1007/978-1-4757-5806-1_6. View

5.
Galli L, Barnes T, Secrest S, Kadowaki T, Burrus L . Porcupine-mediated lipid-modification regulates the activity and distribution of Wnt proteins in the chick neural tube. Development. 2007; 134(18):3339-48. DOI: 10.1242/dev.02881. View