Journal: Glia

Article Title: Myelination and mTOR

doi: 10.1002/glia.23273

Figure Lengend Snippet: mTORC1 and its upstream pathways. A schematic representation of the main components of the mTORC1 pathway and major upstream pathways controlling mTORC1 activity is shown. The red line highlights the major inhibitory feedback loop from mTORC1 to PI3K‐Akt

Article Snippet: How are mTORC1 activity levels in remyelinating cells affecting repair after lesions (McLane et al., )?

Techniques: Activity Assay

Journal: Glia

Article Title: Myelination and mTOR

doi: 10.1002/glia.23273

Figure Lengend Snippet: Molecular events downstream of mTORC1 during cell differentiation and myelin growth. Before onset of myelination, mTORC1 controls differentiation of myelinating cells. In the PNS, it suppresses transiently Krox20 expression via S6K and thus the transition from promyelinating to myelinating SCs. A decline in mTORC1 activity releases this block and allows myelination to proceed. In the CNS, mTORC1 activity promotes differentiation of OLs from OPCs through unknown mechanisms. After onset of myelination, mTORC1 positively regulates myelin production in both the PNS and CNS. In the PNS, mTORC1 signaling increases expression of SREBP1c via the transcription factor RXRγ, while probably promoting SREBP2 activation through post‐translational mechanisms. In the CNS, mTORC1 positively regulates at the transcriptional level expression of SREBP2, but not SREBP1c. Additionally, mTORC1 signaling stimulates translation of MBP. How mTORC1 activity changes during development of SCs with respect to Krox20 levels is graphically indicated in the bottom part of the figure. No analogous information is yet available for OL‐lineage cell development. Dashed lines indicate indirect and/or in detail unknown mechanisms

Article Snippet: How are mTORC1 activity levels in remyelinating cells affecting repair after lesions (McLane et al., )?

Techniques: Cell Differentiation, Expressing, Activity Assay, Blocking Assay, Activation Assay

Journal: Glia

Article Title: Myelination and mTOR

doi: 10.1002/glia.23273

Figure Lengend Snippet: Potential perturbation of mTORC1‐independent targets upon disruption of the TSC complex. Due to feedback inhibition of the upstream pathways, hyperactivation of mTORC1 after disruption of the TSC complex (on the right) has the potential to perturb also mTORC1‐independent targets of Akt and Erk1/2 (“other targets”) leading to different outcomes (symbolized by differently colored arrows). A similar general mechanism appears to underlie paradoxical effects of TSC1 or TSC2 deletion in other cell types. The green halo indicates level of activity. Note that phosphorylation of mTORC1‐independent targets by Akt or Erk1/2 may be either activating or inhibitory

Article Snippet: How are mTORC1 activity levels in remyelinating cells affecting repair after lesions (McLane et al., )?

Techniques: Disruption, Inhibition, Activity Assay, Phospho-proteomics

Journal: Glia

Article Title: Myelination and mTOR

doi: 10.1002/glia.23273

Figure Lengend Snippet: Overview of the outcomes of loss‐ or gain‐of‐function studies of various components of mTORC1 and upstream pathways. The major outcomes of the loss‐ and gain‐of‐function studies on the roles of mTORC1 and the upstream PI3K‐Akt and Mek‐Erk1/2 pathways in PNS and CNS myelination are summarized (Beirowski et al., ; Bercury et al., ; Carson et al., ; Cotter et al., ; Domenech‐Estevez et al., ; Figlia et al., ; Flores et al., ; Fyffe‐Maricich, Karlo, Landreth, & Miller, ; Fyffe‐Maricich, Schott, Karl, Krasno, & Miller, ; Goebbels et al., , ; Ishii, Furusho, & Bansal, ; Ishii, Furusho, Dupree, & Bansal, ; Jeffries et al., ; Jiang et al., ; Lebrun‐Julien et al., ; Napoli et al., ; Newbern et al., ; Norrmén et al., ; Sheean et al., ; Sherman et al., ; Wahl et al., ; Zou et al., , )

Article Snippet: How are mTORC1 activity levels in remyelinating cells affecting repair after lesions (McLane et al., )?

Techniques: