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J Neurosci. 2014 Mar 26;34(13):4466-80. doi: 10.1523/JNEUROSCI.4314-13.2014.

Conditional ablation of raptor or rictor has differential impact on oligodendrocyte differentiation and CNS myelination.

Author information

1
Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, Colorado 80045, and Department of Neurology and Neuroscience, New Jersey Medical School Cancer Center, Rutgers Biomedical and Health Sciences, Newark, New Jersey 07103.

Abstract

During CNS development, oligodendrocytes, the myelinating glia of the CNS, progress through multiple transitory stages before terminating into fully mature cells. Oligodendrocyte differentiation and myelination is a tightly regulated process requiring extracellular signals to converge to elicit specific translational and transcriptional changes. Our lab has previously shown that the protein kinases, Akt and mammalian Target of Rapamycin (mTOR), are important regulators of CNS myelination in vivo. mTOR functions through two distinct complexes, mTOR complex 1 (mTORC1) and mTORC2, by binding to either Raptor or Rictor, respectively. To establish whether the impact of mTOR on CNS myelination results from unique functions of mTORC1 or mTORC2 during CNS myelination, we conditionally ablated either Raptor or Rictor in the oligodendrocyte lineage, in vivo. We show that Raptor (mTORC1) is a positive regulator of developmental CNS mouse myelination when mTORC2 is functional, whereas Rictor (mTORC2) ablation has a modest positive effect on oligodendrocyte differentiation, and very little effect on myelination, when mTORC1 is functional. Also, we show that loss of Raptor in oligodendrocytes results in differential dysmyelination in specific areas of the CNS, with the greatest impact on spinal cord myelination.

KEYWORDS:

Raptor; Rictor; mTOR; oligodendrocyte

PMID:
24671993
PMCID:
PMC3965777
DOI:
10.1523/JNEUROSCI.4314-13.2014
[Indexed for MEDLINE]
Free PMC Article

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