• search hit 1 of 3
Back to Result List

mTORC1 Controls PNS Myelination along the mTORC1-RXR gamma-SREBP-Lipid Biosynthesis Axis in Schwann Cells

Please always quote using this URN: urn:nbn:de:bvb:20-opus-114847
  • Myelin formation during peripheral nervous system (PNS) development, and reformation after injury and in disease, requires multiple intrinsic and extrinsic signals. Akt/mTOR signaling has emerged as a major player involved, but the molecular mechanisms and downstream effectors are virtually unknown. Here, we have used Schwann-cell-specific conditional gene ablation of raptor and rictor, which encode essential components of the mTOR complexes 1 (mTORC1) and 2 (mTORC2), respectively, to demonstrate that mTORC1 controls PNS myelination duringMyelin formation during peripheral nervous system (PNS) development, and reformation after injury and in disease, requires multiple intrinsic and extrinsic signals. Akt/mTOR signaling has emerged as a major player involved, but the molecular mechanisms and downstream effectors are virtually unknown. Here, we have used Schwann-cell-specific conditional gene ablation of raptor and rictor, which encode essential components of the mTOR complexes 1 (mTORC1) and 2 (mTORC2), respectively, to demonstrate that mTORC1 controls PNS myelination during development. In this process, mTORC1 regulates lipid biosynthesis via sterol regulatory element-binding proteins (SREBPs). This course of action is mediated by the nuclear receptor RXRg, which transcriptionally regulates SREBP1c downstream of mTORC1. Absence of mTORC1 causes delayed myelination initiation as well as hypomyelination, together with abnormal lipid composition and decreased nerve conduction velocity. Thus, we have identified the mTORC1-RXR gamma-SREBP axis controlling lipid biosynthesis as a major contributor to proper peripheral nerve function.show moreshow less

Download full text files

Export metadata

Additional Services

Share in Twitter Search Google Scholar Statistics
Metadaten
Author: Camilla Norrmen, Gianluca Figlia, Frederic Lebrun-Julien, Jorge A. Pereira, Martin Trötzmüller, Harald C. Köfeler, Ville Rantanen, Carsten Wessig, Anne-Lieke F. van Deijk, August B. Smit, Mark H. G. Verheijen, Markus A. Rüegg, Michael N. Hall, Ueli Suter
URN:urn:nbn:de:bvb:20-opus-114847
Document Type:Journal article
Faculties:Medizinische Fakultät / Neurologische Klinik und Poliklinik
Language:English
Parent Title (English):Cell Reports
ISSN:2211-1247
Year of Completion:2014
Volume:9
Issue:2
Pagenumber:646-660
Source:Cell Reports 9, 646–660. DOI:10.1016/j.celrep.2014.09.001
DOI:https://doi.org/10.1016/j.celrep.2014.09.001
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=25310982
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:CNS Myelination; COMPLEX 1; SREBP; axonal integrity; element; growth; mice; peripheral nervous-system; protein; rat hepatocytes
Release Date:2015/07/10
Licence (German):License LogoCC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitung