P90 Ribosomal s6 kinase 2 negatively regulates axon growth in motoneurons.
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.
Fischer
Matthias
M
Institute for Clinical Neurobiology, University of Würzburg, 97080 Würzburg, Germany. fischer_m2@klinik.uni-wuerzburg.de
Pereira
Patricia Marques
PM
Holtmann
Bettina
B
Simon
Christian M
CM
Hanauer
Andre
A
Heisenberg
Martin
M
Sendtner
Michael
M
D000818:Animals; D001369:Axons / Q000502:physiology*; D002470:Cell Survival; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology
D038744:Ribosomal Protein S6 Kinases, 90-kDa; C069330:ribosomal protein S6 kinase, 90kDa, polypeptide 3