Glycosphingolipid metabolic reprogramming drives neural differentiation
| Autor: | Alberto Luini, Riccardo Rizzo, Salvatore Fioriniello, Vittorio Maglione, Ilaria Granata, Kei Hori, Maurizio D'Esposito, Mario Rosario Guarracino, Serena Capasso, Mikio Hoshino, Domenico Russo, Ludger Johannes, Giovanni D'Angelo, Floriana Della Ragione, Francesco Scalabrì, Eiji Sugiyama, Lucia Sticco, Mitsutoshi Setou, Gian Carlo Bellenchi, Roberto De Gregorio |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Epigenomics sialyltransferase nervous system development bistability neural differentiation Regulator Gene Expression nerve cell differentiation mental disease ganglioside glycosphingolipid GM3 synthase synthetase unclassified drug AUTS2 protein human haematoside synthetase histone protein sialyltransferase Article AUTS2 gene epigenetics gene gene expression gene function human lipid metabolism lipogenesis metabolic regulation neuropathology nonhuman priority journal promoter region regulatory mechanism cell differentiation drug effect gene silencing genetics HeLa cell line metabolism nerve cell nuclear reprogramming physiology Cell Differentiation Cellular Reprogramming Gangliosides Gene Silencing Glycosphingolipids HeLa Cells Histones Humans Neurodevelopmental Disorders Neurogenesis Neurons Promoter Regions Genetic Proteins Sialyltransferases AUTS2 glycosphingolipids chemistry.chemical_compound Gene expression News & Views General Neuroscience Cell Differentiation Glycosphingolipid Cell biology lipids (amino acids peptides and proteins) Reprogramming Neural development Biology digestive system Article General Biochemistry Genetics and Molecular Biology Promoter Regions 03 medical and health sciences Genetic Epigenetics Molecular Biology General Immunology and Microbiology Mechanism (biology) AUTS2 protein nutritional and metabolic diseases carbohydrates (lipids) Cytoskeletal Proteins 030104 developmental biology chemistry physiology Function (biology) Transcription Factors |
| Zdroj: | EMBO journal 37 (2017): e97674. doi:10.15252/embj.201797674 info:cnr-pdr/source/autori:Russo, Domenico; Della Ragione, Floriana; Rizzo, Riccardo; Sugiyama, Eiji; Scalabrì, Francesco; Hori, Kei; Capasso, Serena; Sticco, Lucia; Fioriniello, Salvatore; De Gregorio, Roberto; Granata, Ilaria; Guarracino, Mario R.; Maglione, Vittorio; Johannes, Ludger; Bellenchi, Gian Carlo; Hoshino, Mikio; Setou, Mitsutoshi; D'Esposito, Maurizio; Luini, Alberto; D'Angelo, Giovanni/titolo:Glycosphingolipid metabolic reprogramming drives neural differentiation/doi:10.15252%2Fembj.201797674/rivista:EMBO journal (Print)/anno:2017/pagina_da:e97674/pagina_a:/intervallo_pagine:e97674/volume:37 |
| ISSN: | 1460-2075 |
| DOI: | 10.15252/embj.201797674 |
| Popis: | Neural development is accomplished by differentiation events leading to metabolic reprogramming. Glycosphingolipid metabolism is reprogrammed during neural development with a switch from globo‐ to ganglio‐series glycosphingolipid production. Failure to execute this glycosphingolipid switch leads to neurodevelopmental disorders in humans, indicating that glycosphingolipids are key players in this process. Nevertheless, both the molecular mechanisms that control the glycosphingolipid switch and its function in neurodevelopment are poorly understood. Here, we describe a self‐contained circuit that controls glycosphingolipid reprogramming and neural differentiation. We find that globo‐series glycosphingolipids repress the epigenetic regulator of neuronal gene expression AUTS2. AUTS2 in turn binds and activates the promoter of the first and rate‐limiting ganglioside‐producing enzyme GM3 synthase, thus fostering the synthesis of gangliosides. By this mechanism, the globo–AUTS2 axis controls glycosphingolipid reprogramming and neural gene expression during neural differentiation, which involves this circuit in neurodevelopment and its defects in neuropathology. |
| Databáze: | OpenAIRE |
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