Monday, 21 July 2014

Balance of myelination

Lebrun-Julien F, Bachmann L, Norrmén C, Trötzmüller M, Köfeler H, Rüegg MA, Hall MN, Suter U. Balanced mTORC1 Activity in Oligodendrocytes Is Required for Accurate CNS Myelination. J Neurosci. 2014; 34(25):8432-48. doi: 10.1523/JNEUROSCI.1105-14.2014.

The mammalian target of rapamycin (mTOR) pathway integrates multiple signals and regulates crucial cell functions via the molecular complexes mTORC1 and mTORC2. These complexes are functionally dependent on their raptor (mTORC1) or rictor (mTORC2) subunits. mTOR has been associated with oligodendrocyte differentiation and myelination downstream of the PI3K/Akt pathway, but the functional contributions of individual complexes are largely unknown. We show, by oligodendrocyte-specific genetic deletion of Raptor and/or Rictor in the mouse, that CNS myelination is mainly dependent on mTORC1 function, with minor mTORC2 contributions. Myelin-associated lipogenesis and protein gene regulation are strongly reliant on mTORC1. We found that also oligodendrocyte-specific overactivation of mTORC1, via ablation of tuberous sclerosis complex 1 (TSC1), causes hypomyelination characterized by downregulation of Akt signalling and lipogenic pathways. Our data demonstrate that a delicately balanced regulation of mTORC1 activation and action in oligodendrocytes is essential for CNS myelination, which has practical overtones for understanding CNS myelin disorders.

Mammalian target of rapamycin, mTOR, is a serine/threonine protein kinase that regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, and transcription.The role of mTORC1 is to activate production of proteins. In order for cells to grow and proliferate by manufacturing more proteins, the cells must ensure that they have the resources available for protein production. Thus, for protein production, and therefore mTORC1 activation, cells must have adequate energy resources, nutrient availability, oxygen abundance, and proper growth factors in order for protein translation to begin. This paper shows that a signalling molecule can control myelination lack of it promotes myelination and to much of it stops myelination. In the past couple of years we have found many factors that may promote remyelination. Some of these are in a fine balance between having one effect or stimulating another afect. which is typical of many biological processes.   

2 comments:

  1. Very infomative. Please could you update :-)

    ReplyDelete
  2. Really interesting. Please could you update :-)
    Thanks

    John

    ReplyDelete

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