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Maf links Neuregulin1 signaling to cholesterol synthesis in myelinating Schwann cells

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Item Type:Article
Title:Maf links Neuregulin1 signaling to cholesterol synthesis in myelinating Schwann cells
Creators Name:Kim, M. and Wende, H. and Walcher, J. and Kühnemund, J. and Cheret, C. and Kempa, S. and McShane, E. and Selbach, M. and Lewin, G.R. and Birchmeier, C.
Abstract:Cholesterol is a major constituent of myelin membranes, which insulate axons and allow saltatory conduction. Therefore, Schwann cells, the myelinating glia of the peripheral nervous system, need to produce large amounts of cholesterol. Here, we define a crucial role of the transcription factor Maf in myelination and cholesterol biosynthesis and show that Maf acts downstream from Neuregulin1 (Nrg1). Maf expression is induced when Schwann cells begin myelination. Genetic ablation of Maf resulted in hypomyelination that resembled mice with defective Nrg1 signaling. Importantly, loss of Maf or Nrg1 signaling resulted in a down-regulation of the cholesterol synthesis program, and Maf directly binds to enhancers of cholesterol synthesis genes. Furthermore, we identified the molecular mechanisms by which Nrg1 signaling regulates Maf levels. Transcription of Maf depends on calmodulin-dependent kinases downstream from Nrg1, whereas Nrg1-MAPK signaling stabilizes Maf protein. Our results delineate a novel signaling cascade regulating cholesterol synthesis in myelinating Schwann cells.
Keywords:Schwann Cell, Myelination, Maf, Neuregulin1, Cholesterol, Animals, Mice, Rats, Wistar Rats
Source:Genes & Development
ISSN:0890-9369
Publisher:Cold Spring Harbor Laboratory Press (U.S.A.)
Volume:32
Number:9-10
Page Range:645-657
Date:10 May 2018
Additional Information:Erratum in: Genes Dev 32(15-16): 1101.
Official Publication:https://doi.org/10.1101/gad.310490.117
PubMed:View item in PubMed

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