amanitins and acetylleucyl-leucyl-norleucinal

Growth cones contain mRNAs, translation machinery, and, as we report here, protein degradation machinery. We show that isolated retinal growth cones immediately lose their ability to turn in a chemotropic gradient of netrin-1 or Sema3A when translation is inhibited. Translation inhibition also prevents Sema3A-induced collapse, while LPA-induced collapse is not affected. Inhibition of proteasome function blocks responses to netrin-1 and LPA but does not affect Sema3A responses. We further demonstrate in isolated growth cones that netrin-1 and Sema3A activate translation initiation factors and stimulate a marked rise in protein synthesis within minutes, while netrin-1 and LPA elicit similar rises in ubiquitin-protein conjugates. These results suggest that guidance molecules steer axon growth by triggering rapid local changes in protein levels in growth cones.

Topics: Amanitins; Animals; Carrier Proteins; Cysteine Endopeptidases; Cysteine Proteinase Inhibitors; Drosophila Proteins; Eukaryotic Initiation Factor-4E; Eye Proteins; Glycoproteins; Growth Cones; Leupeptins; Lipopolysaccharides; Multienzyme Complexes; Nerve Growth Factors; Netrin-1; Nucleic Acid Synthesis Inhibitors; Peptide Initiation Factors; Phosphatidylinositol 3-Kinases; Phosphoproteins; Proteasome Endopeptidase Complex; Protein Biosynthesis; Receptor Protein-Tyrosine Kinases; Retina; Semaphorin-3A; Tumor Suppressor Proteins; Ubiquitin; Xenopus