The Lysosomal Transcription Factor TFEB Represses Myelination Downstream of the Rag-Ragulator Complex.

ABSTRACT: Myelin allows for fast and efficient axonal conduction, but much remains to be determined about the mechanisms that regulate myelin formation. To investigate the genetic basis of myelination, we carried out a genetic screen using zebrafish. Here, we show that the lysosomal G protein RagA is essential for CNS myelination. In rraga^-/- mutant oligodendrocytes, target genes of the lysosomal transcription factor Tfeb are upregulated, consistent with previous evidence that RagA represses Tfeb activity. Loss of Tfeb function is sufficient to restore myelination in RagA mutants, indicating that hyperactive Tfeb represses myelination. Conversely, tfeb^-/- single mutants exhibit ectopic myelin, further indicating that Tfeb represses myelination during development. In a mouse mod

SUBMITTER: Meireles AM 

PROVIDER: S-EPMC6250074 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature