PUBLICATION
Oligodendrocyte development and myelin sheath formation are regulated by the antagonistic interaction between the Rag-Ragulator complex and TFEB
- Authors
- Bouchard, E.L., Meireles, A.M., Talbot, W.S.
- ID
- ZDB-PUB-231002-180
- Date
- 2023
- Source
- Glia 72(2): 289-299 (Journal)
- Registered Authors
- Talbot, William S.
- Keywords
- RagA, TFEB, myelin, oligodendrocyte, zebrafish
- MeSH Terms
-
- Animals
- Axons/metabolism
- Central Nervous System/metabolism
- Monomeric GTP-Binding Proteins*/metabolism
- Myelin Sheath*/metabolism
- Oligodendroglia*/metabolism
- Spinal Cord/metabolism
- Zebrafish
- Zebrafish Proteins*/metabolism
- PubMed
- 37767930 Full text @ Glia
Citation
Bouchard, E.L., Meireles, A.M., Talbot, W.S. (2023) Oligodendrocyte development and myelin sheath formation are regulated by the antagonistic interaction between the Rag-Ragulator complex and TFEB. Glia. 72(2):289-299.
Abstract
Myelination by oligodendrocytes is critical for fast axonal conduction and for the support and survival of neurons in the central nervous system. Recent studies have emphasized that myelination is plastic and that new myelin is formed throughout life. Nonetheless, the mechanisms that regulate the number, length, and location of myelin sheaths formed by individual oligodendrocytes are incompletely understood. Previous work showed that the lysosomal transcription factor TFEB represses myelination by oligodendrocytes and that the RagA GTPase inhibits TFEB, but the step or steps of myelination in which TFEB plays a role have remained unclear. Here, we show that TFEB regulates oligodendrocyte differentiation and also controls the length of myelin sheaths formed by individual oligodendrocytes. In the dorsal spinal cord of tfeb mutants, individual oligodendrocytes produce myelin sheaths that are longer than those produced by wildtype cells. Transmission electron microscopy shows that there are more myelinated axons in the dorsal spinal cord of tfeb mutants than in wildtype animals, but no significant change in axon diameter. In contrast to tfeb mutants, oligodendrocytes in rraga mutants produce shorter myelin sheaths. The sheath length in rraga; tfeb double mutants is not significantly different from wildtype, consistent with the antagonistic interaction between RagA and TFEB. Finally, we find that the GTPase activating protein Flcn and the RagCa and RagCb GTPases are also necessary for myelination by oligodendrocytes. These findings demonstrate that TFEB coordinates myelin sheath length and number during myelin formation in the central nervous system.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping