Protein synthesis dependence of growth cone collapse induced by different Nogo-A-domains.
BACKGROUND
The 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.


RESULTS
We 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.


CONCLUSIONS
Growth 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.
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
Richard
R
Manns
Brain Research Institute, University of Zurich and Department of Health Sciences and Technology, Swiss Federal Institute of Technology, Zurich, Switzerland.
Andre
A
Schmandke
Brain Research Institute, University of Zurich and Department of Health Sciences and Technology, Swiss Federal Institute of Technology, Zurich, Switzerland.
Antonio
A
Schmandke
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
Prem
P
Jareonsettasin
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
Geoffrey
G
Cook
Brain Research Institute, University of Zurich and Department of Health Sciences and Technology, Swiss Federal Institute of Technology, Zurich, Switzerland.
Martin E
ME
Schwab
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
Christine
C
Holt
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
Roger
R
Keynes
D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D002642:Chick Embryo; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007797:Laminin; D007976:Leupeptins / Q000494:pharmacology; D009185:Myelin Proteins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology*; D000070798:Nogo Proteins; D011107:Polylysine; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects*; D017434:Protein Structure, Tertiary; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction; D046509:Tissue Culture Techniques; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
D007797:Laminin; D007976:Leupeptins; D009185:Myelin Proteins; D000070798:Nogo Proteins; D061988:Proteasome Inhibitors; D011500:Protein Synthesis Inhibitors; D011994:Recombinant Proteins; C063261:acetylleucyl-leucyl-norleucinal; D011107:Polylysine; D000841:Anisomycin; D046988:Proteasome Endopeptidase Complex; D020742:rhoA GTP-Binding Protein