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Myelin gene Regulatory Factor

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Myelin gene Regulatory Factor ( MRF)is a protein] of critical importance in the development and maintenance of myelin sheaths.[1]

The expression of MRF is specific to mature, myelinating oligodendrocytes in the CNS.[2] It has been shown to be critical for the maintenance of myelin by these cells. Following ablation of MRF the expression of myelin genes such as Proteolipid protein, Myelin basic protein, Myelin-associated glycoprotein and Myelin oligodendrocyte glycoprotein drops rapidly. Therefore, MRF is a key regulator and likely a direct activator of the expression of these genes.[1]

Biological relevanceEdit

Mice that lose MRF during adulthood present with a severe demyelination similar to that seen in animal models of multiple sclerosis. This underlines the importance of an active renewal of proteins in the myelin sheath. Further, the activity of MRF increases during remyelination, suggesting it has a critical role in this process.[1]

Congruently, it has been shown that animals with repressed MRF in a proportion of oligodendrocyte precursor cells showed a delayed functional recovery from spinal cord injury.[3]

MRF has been shown to be significantly downregulated in a mouse model carrying the same mutation in the NPC1 protein that is underlying Niemann-Pick type C1 disease, a neurodegenerative process in which dysmyelination is a main pathogenic factor. A perturbation of oligodendrocyte maturation and myelination therefore might be an underlying reason for the neurological deficits.[4]

MRF-like proteinsEdit

MRF is encoded by the MRF/GM98 gene in mice and by the C11orf9 gene in humans.[5] The family of MRF-like-proteins also contains the orthologues pqn-47 from C. elegans and MrfA from Dictyostelium.[6] All orthologues have a domain of high homology to the Saccharomyces cerevisiae protein Ndt80 and therefore likely act as a transcription factor.


ReferencesEdit

  1. ^ a b c Koenning, Matthias; Jackson, Stacey Hay, Curtis M. Faux, Clare Kilpatrick, Trevor J. Willingham, Melanie Emery, Ben (September 5, 2012). "Myelin Gene Regulatory Factor Is Required for Maintenance of Myelin and Mature Oligodendrocyte Identity in the Adult CNS". The Journal of Neuroscience 32 (36): 12528–12542 . doi:10.1523/jneurosci.1069-12.2012. PMID 22956843.
  2. ^ Cahoy, J. D.; Emery, B.; Kaushal, A.; Foo, L. C.; Zamanian, J. L.; Christopherson, K. S.; Xing, Y.; Lubischer, J. L. et al. (2008). "A Transcriptome Database for Astrocytes, Neurons, and Oligodendrocytes: A New Resource for Understanding Brain Development and Function". Journal of Neuroscience 28 (1): 264–278. doi:10.1523/JNEUROSCI.4178-07.2008. PMID 18171944.
  3. ^ Duncan, G. J.; Plemel, J. R.; Hilton, B. J.; Liu, J.; Kramer, J. K.; Kim, J.; Mao, S.; Tetzlaff, W. (2011). "MYELIN GENE REGULATORY FACTOR KNOCKOUT DELAYS FUNCTIONAL RECOVERY FROM SPINAL CORD INJURY". Glia 59: S60–S60.
  4. ^ Yan, X.; Lukas, J.; Witt, M.; Wree, A.; Hubner, R.; Frech, M.; Kohling, R.; Rolfs, A.; Luo, J. (2011/09/23). "Decreased expression of myelin gene regulatory factor in Niemann-Pick type C 1 mouse". Metab Brain Dis 26 (4): 299–306. doi:10.1007/s11011-011-9263-9. PMID 21938520.
  5. ^ "MRF" (in english). 13. p. UnitProtKB.
  6. ^ Senoo, Hiroshi; Wang, Hong-Yu ; Araki, Tsuyoshi ; Williams, Jeffrey G ; Fukuzawa, Masashi (July 20,2012). "An orthologue of the Myelin-gene Regulatory Transcription Factor regulates Dictyostelium prestalk differentiation". Int J Dev Biol 56 (5): 325–34. doi:10.1387/ijdb.120030jw.

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