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Balanced mTORC1 activity in oligodendrocytes is required for accurate CNS myelination

Lebrun-Julien, F. and Bachmann, L. and Norrmén, C. and Trötzmüller, M. and Köfeler, H. and Rüegg, M. A. and Hall, M. N. and Suter, U.. (2014) Balanced mTORC1 activity in oligodendrocytes is required for accurate CNS myelination. Journal of Neuroscience, 34 (25). pp. 8432-8448.

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Hall)
05 Faculty of Science > Departement Biozentrum > Neurobiology > Pharmacology/Neurobiology (Rüegg)
UniBasel Contributors:Hall, Michael N. and Rüegg, Markus A.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Society for Neuroscience
ISSN:0270-6474
e-ISSN:1529-2401
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:09 Nov 2017 09:19
Deposited On:18 Jul 2014 09:10

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