title: Conditional ablation of raptor or rictor has differential impact on oligodendrocyte differentiation and CNS myelination.
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.
authors.affiliation: 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.
authors.forename: Kathryn K
authors.initials: KK
authors.lastname: Bercury
authors.forename: JinXiang
authors.initials: J
authors.lastname: Dai
authors.forename: Hilary H
authors.initials: HH
authors.lastname: Sachs
authors.forename: Jared T
authors.initials: JT
authors.lastname: Ahrendsen
authors.forename: Teresa L
authors.initials: TL
authors.lastname: Wood
authors.forename: Wendy B
authors.initials: WB
authors.lastname: Macklin
mesh_terms: D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002452:Cell Count; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002490:Central Nervous System / Q000166:cytology* / Q000502:physiology; D003337:Corpus Callosum / Q000166:cytology* / Q000648:ultrastructure; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000378:metabolism* / Q000648:ultrastructure; D009836:Oligodendroglia / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D000076223:Regulatory-Associated Protein of mTOR; D015398:Signal Transduction / Q000502:physiology; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D000076223:Regulatory-Associated Protein of mTOR; C540162:Rptor protein, mouse; C525637:rictor protein, mouse; D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; C571338:Cnp protein, mouse; D001616:beta-Galactosidase
keywords: Raptor; Rictor; mTOR; oligodendrocyte