P90 Ribosomal s6 kinase 2 negatively regulates axon growth in motoneurons.

Matthias Fischer 1 Patricia Marques Pereira 2 Bettina Holtmann 1 Christian Simon 1 Andre Hanauer 2 Martin Heisenberg 3 Michael Sendtner 1
1 Institute for Clinical Neurobiology
2 IGBMC - Institut de génétique et biologie moléculaire et cellulaire
3 Institute for Genetics and Neurobiology
Abstract : Mutations in Ribosomal s6 kinase 2 (Rsk2) are associated with severe neuronal dysfunction in Coffin-Lowry syndrome (CLS) patients, flies and mice. So far, the mechanisms of how Rsk2 regulates development, maintenance and activity of neurons are not understood. We have investigated the consequences of Rsk2 deficiency in mouse spinal motoneurons. Survival of isolated Rsk2 deficient motoneurons is not reduced, but these cells grow significantly longer neurites. Conversely, overexpression of a constitutively active form of Rsk2 leads to reduced axon growth. Increased axon growth in Rsk2 deficient neurons was accompanied by higher Erk 1/2 phosphorylation, and the knockout phenotype could be rescued by pharmacological inhibition of MAPK/Erk kinase (Mek). These data indicate that Rsk2 negatively regulates axon elongation via the MAPK pathway. Thus, the functional defects observed in the nervous system of CLS patients and animal models with Rsk2 deficiency might be caused by dysregulated neurite growth rather than primary neurodegeneration.
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Molecular and Cellular Neuroscience, Elsevier, 2009, 42 (2), pp.134-41. 〈10.1016/j.mcn.2009.06.006〉
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http://www.hal.inserm.fr/inserm-00420800
Contributeur : Maité Peney <>
Soumis le : mardi 29 septembre 2009 - 16:33:57
Dernière modification le : jeudi 25 janvier 2018 - 11:42:02

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Matthias Fischer, Patricia Marques Pereira, Bettina Holtmann, Christian Simon, Andre Hanauer, et al.. P90 Ribosomal s6 kinase 2 negatively regulates axon growth in motoneurons.. Molecular and Cellular Neuroscience, Elsevier, 2009, 42 (2), pp.134-41. 〈10.1016/j.mcn.2009.06.006〉. 〈inserm-00420800〉

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