Protein Synthesis Dependence of Growth Cone Collapse Induced by Different Nogo-A-Domains |
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| Authors: | Richard Manns Andre Schmandke Antonio Schmandke Prem Jareonsettasin Geoffrey Cook Martin E Schwab Christine Holt Roger Keynes |
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| Institution: | 1. Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.; 2. Brain Research Institute, University of Zurich and Department of Health Sciences and Technology, Swiss Federal Institute of Technology, Zurich, Switzerland.; National Institutes of Health (NIH), United States of America, |
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| Abstract: | BackgroundThe protein Nogo-A regulates axon growth in the developing and mature nervous system, and this is carried out by two distinct domains in the protein, Nogo-A-Δ20 and Nogo-66. The differences in the signalling pathways engaged in axon growth cones by these domains are not well characterized, and have been investigated in this study.Methodology/Principal FindingsWe analyzed growth cone collapse induced by the Nogo-A domains Nogo-A-Δ20 and Nogo-66 using explanted chick dorsal root ganglion neurons growing on laminin/poly-lysine substratum. Collapse induced by purified Nogo-A-Δ20 peptide is dependent on protein synthesis whereas that induced by Nogo-66 peptide is not. Nogo-A-Δ20-induced collapse is accompanied by a protein synthesis-dependent rise in RhoA expression in the growth cone, but is unaffected by proteasomal catalytic site inhibition. Conversely Nogo-66-induced collapse is inhibited ∼50% by proteasomal catalytic site inhibition.Conclusion/SignificanceGrowth cone collapse induced by the Nogo-A domains Nogo-A-Δ20 and Nogo-66 is mediated by signalling pathways with distinguishable characteristics concerning their dependence on protein synthesis and proteasomal function. |
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