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Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Lebrun-Julien, F; Bachmann, L; Norrmén, C; Trötzmüller, M; Köfeler, H; Rüegg, MA; Hall, MN; Suter, U.
Balanced mTORC1 activity in oligodendrocytes is required for accurate CNS myelination.
J NEUROSCI. 2014; 34(25): 8432-8448.
Doi: 10.1523/JNEUROSCI.1105-14.2014
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- Co-Autor*innen der Med Uni Graz
- Köfeler Harald
- Trötzmüller Martin
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- Abstract:
- The mammalian target of rapamycin (mTOR) pathway integrates multiple signals and regulates crucial cell functions via the molecular complexes mTORC1 and mTORC2. These complexes are functionally dependent on their raptor (mTORC1) or rictor (mTORC2) subunits. mTOR has been associated with oligodendrocyte differentiation and myelination downstream of the PI3K/Akt pathway, but the functional contributions of individual complexes are largely unknown. We show, by oligodendrocyte-specific genetic deletion of Rptor and/or Rictor in the mouse, that CNS myelination is mainly dependent on mTORC1 function, with minor mTORC2 contributions. Myelin-associated lipogenesis and protein gene regulation are strongly reliant on mTORC1. We found that also oligodendrocyte-specific overactivation of mTORC1, via ablation of tuberous sclerosis complex 1 (TSC1), causes hypomyelination characterized by downregulation of Akt signaling and lipogenic pathways. Our data demonstrate that a delicately balanced regulation of mTORC1 activation and action in oligodendrocytes is essential for CNS myelination, which has practical overtones for understanding CNS myelin disorders. Copyright © 2014 the authors 0270-6474/14/348432-17$15.00/0.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Central Nervous System - metabolism Central Nervous System - pathology
- Female -
- Male -
- Mice -
- Mice, Knockout -
- Mice, Transgenic -
- Multiprotein Complexes - metabolism
- Nerve Fibers, Myelinated - metabolism Nerve Fibers, Myelinated - pathology
- Oligodendroglia - metabolism Oligodendroglia - pathology
- Spinal Cord - metabolism Spinal Cord - pathology
- TOR Serine-Threonine Kinases - metabolism
- Find related publications in this database (Keywords)
- mTOR
- myelin
- oligodendrocytes
- TSC1
- TSC2
- tuberous sclerosis