Conditional ablation of raptor or rictor has differential impact on oligodendrocyte differentiation and CNS myelination
| Autor: | Jinxiang Dai, Jared T. Ahrendsen, Hilary H. Sachs, Kathryn K. Bercury, Teresa L. Wood, Wendy B. Macklin |
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| Rok vydání: | 2014 |
| Předmět: |
Central Nervous System
Male Cellular differentiation Central nervous system Cell Count Mice Transgenic mTORC1 Biology mTORC2 2' 3'-Cyclic-nucleotide 3'-phosphodiesterase Corpus Callosum Mice 2' 3'-Cyclic Nucleotide 3'-Phosphodiesterase medicine Animals PI3K/AKT/mTOR pathway Myelin Sheath Adaptor Proteins Signal Transducing General Neuroscience Oligodendrocyte differentiation Cell Differentiation Regulatory-Associated Protein of mTOR Articles beta-Galactosidase Oligodendrocyte Mice Inbred C57BL Oligodendroglia medicine.anatomical_structure Rapamycin-Insensitive Companion of mTOR Protein Gene Expression Regulation Female Carrier Proteins Neuroscience Signal Transduction |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience. 34(13) |
| ISSN: | 1529-2401 |
| Popis: | 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 myelinationin 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. |
| Databáze: | OpenAIRE |
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