Maf links Neuregulin1 signaling to cholesterol synthesis in myelinating Schwann cells

Genes & Development
Minchul KimCarmen Birchmeier

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.

References

Nov 23, 1995·Nature·D Meyer, C Birchmeier
Dec 16, 1997·Trends in Biochemical Sciences·V Blank, N C Andrews
Mar 31, 1999·Proceedings of the National Academy of Sciences of the United States of America·J I KimL H Glimcher
Mar 21, 2000·Genesis : the Journal of Genetics and Development·O VoiculescuS Schneider-Maunoury
Mar 8, 2000·The Journal of Cell Biology·A N GarrattC Birchmeier
Mar 23, 2000·Journal of Neurology, Neurosurgery, and Psychiatry·S SanderJ D Pollard
Sep 3, 2002·American Journal of Respiratory Cell and Molecular Biology·Jinbo Liu, Jeffrey A Kern
Jun 5, 2003·Genes & Development·Martine JaegleDies Meijer
Jul 3, 2003·Nature Reviews. Molecular Cell Biology·Michael J BerridgeH Llewelyn Roderick
Mar 27, 2004·Science·Galin V MichailovKlaus-Armin Nave
Mar 29, 2005·Nature Neuroscience·Gesine SaherKlaus-Armin Nave
Mar 31, 2005·Current Biology : CB·David A LyonsWilliam S Talbot
Mar 31, 2005·Molecular and Cellular Biology·Xiang-Jiao Yang, Serge Grégoire
Sep 1, 2005·Neuron·Carla TaveggiaJames L Salzer
Sep 2, 2005·Nature Reviews. Neuroscience·Kristjan R Jessen, Rhona Mirsky
Sep 23, 2006·Science·Michael WillemChristian Haass
Sep 23, 2008·Glia·Michael A ChernousovSidney Strickland
Jan 10, 2009·Nature Protocols·Da Wei HuangRichard A Lempicki
Jun 23, 2009·Gene·Megumi NakamuraSatoru Takahashi
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Katja S GrossmannCarmen Birchmeier
Dec 2, 2009·Proceedings of the National Academy of Sciences of the United States of America·Mark H G VerheijenAugust B Smit
Sep 14, 2010·Seminars in Cell & Developmental Biology·Jason Newbern, Carmen Birchmeier
Jan 12, 2011·Neuron·Jason M NewbernWilliam D Snider
Feb 16, 2011·Glia·Peter Arthur-FarrajKristján R Jessen
Feb 4, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Diane L ShermanPeter J Brophy
Apr 11, 2012·EMBO Molecular Medicine·Sandra GoebbelsKlaus-Armin Nave
Apr 12, 2012·Nucleic Acids Research·Rajini SrinivasanJohn Svaren
May 15, 2015·Glia·Camila Lopez-AnidoJohn Svaren
Apr 22, 2016·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Enric Domènech-EstévezJames L Salzer
Dec 9, 2016·Current Opinion in Neurobiology·Amy L Herbert, Kelly R Monk

❮ Previous
Next ❯

Citations

Oct 2, 2019·The Journal of Experimental Medicine·Morgan E ParkerMaria Ciofani
Apr 2, 2020·Cells·Yannick PoitelonSophie Belin
Apr 14, 2020·Developmental Neurobiology·Emma R WilsonM Laura Feltri
Nov 17, 2020·Frontiers in Cell and Developmental Biology·Simon VermeirenSimon Desiderio
Nov 5, 2020·Wiley Interdisciplinary Reviews. Developmental Biology·Anoohya N MuppiralaSarah C Petersen

❮ Previous
Next ❯

Related Concepts

Related Feeds

Brain developing: Influences & Outcomes

This feed focuses on influences that affect the developing brain including genetics, fetal development, prenatal care, and gene-environment interactions. Here is the latest research in this field.

© 2022 Meta ULC. All rights reserved