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

ABSTRACT:

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-?20 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 findings

We analyzed growth cone collapse induced by the Nogo-A domains Nogo-A-?20 and Nogo-66 using explanted chick dorsal root ganglion neurons growing on laminin/poly-lysine substratum. Collapse induced by purified Nogo-A-?20 peptide is dependent on protein synthesis whereas that induced by Nogo-66 peptide is not. Nogo-A-?20-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/significance

Growth cone collapse induced by the Nogo-A domains Nogo-A-?20 and Nogo-66 is mediated by signalling pathways with distinguishable characteristics concerning their dependence on protein synthesis and proteasomal function.

SUBMITTER: Manns R 

PROVIDER: S-EPMC3906062 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature