RT Journal Article
SR Electronic
T1 Conditional Ablation of Raptor or Rictor Has Differential Impact on Oligodendrocyte Differentiation and CNS Myelination
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 4466
OP 4480
DO 10.1523/JNEUROSCI.4314-13.2014
VO 34
IS 13
A1 Kathryn K. Bercury
A1 JinXiang Dai
A1 Hilary H. Sachs
A1 Jared T. Ahrendsen
A1 Teresa L. Wood
A1 Wendy B. Macklin
YR 2014
UL http://www.jneurosci.org/content/34/13/4466.abstract
AB 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.