As a cell membrane component and signaling molecule, lipids are essential for the development and function of the nervous system. Mutations in a variety of genes involved in lipid metabolism lead to neurological diseases. However, there are many kinds of lipids and they are transformed into each other in the anabolic pathway. Which lipids are involved in the regulation of neural development and its related regulatory mechanisms are major scientific issues in the field of neurobiology.

Zhang Yongqing, a researcher at the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, used a traditional model of fruit flies as a material to discover that multiple genes regulate the growth of synapses in the glycosphingolipid (GSL) synthesis pathway. Further genetic analysis combined with lipid-specific antibody staining revealed that GSL mannose-glucose ceramide (MacCer) promotes synaptic growth. GSL assembles lipid rafts with sterols on biofilms. Through pharmacological experiments combined with genetic analysis, it was found that MacCer promotes synaptic growth dependent on lipid rafts. Many proteins bind to lipid rafts and participate in signal transduction.

Through molecular simulation and lipid biochemical tests, it was found that a short peptide containing 15 amino acids in Wg can specifically Combined with MacCer. Further in vivo experiments demonstrated that the combination of them affects the colocalization of MacCer and Wg and regulates the growth of synapses. In summary, the study found for the first time that glycosphingolipids MacCer promotes synaptic growth by regulating Wg signaling pathway.

The results of the study were published online on October 25th in the international mainstream journal eLife (DOI: https://doi.org/10.7554/eLife.38183.001). The research was supported by the Ministry of Science and Technology, the National Natural Science Foundation of China and the Chinese Academy of Sciences.

Source: Institute of Genetics and Developmental Biology

Time: 2018.10.29