Chemotropic responses of retinal growth cones mediated by rapid local protein synthesis and degradation

Neuron. 2001 Dec 20;32(6):1013-26. doi: 10.1016/s0896-6273(01)00551-7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amanitins / pharmacology
  • Animals
  • Carrier Proteins / metabolism
  • Cysteine Endopeptidases / metabolism
  • Cysteine Proteinase Inhibitors / pharmacology
  • Drosophila Proteins*
  • Eukaryotic Initiation Factor-4E
  • Eye Proteins / genetics*
  • Eye Proteins / metabolism*
  • Glycoproteins / pharmacology
  • Growth Cones / physiology*
  • Leupeptins / pharmacology
  • Lipopolysaccharides / pharmacology
  • Multienzyme Complexes / antagonists & inhibitors
  • Multienzyme Complexes / metabolism
  • Nerve Growth Factors / pharmacology
  • Netrin-1
  • Nucleic Acid Synthesis Inhibitors / pharmacology
  • Peptide Initiation Factors / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoproteins / metabolism
  • Proteasome Endopeptidase Complex
  • Protein Biosynthesis / drug effects
  • Protein Biosynthesis / physiology*
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Retina / cytology*
  • Retina / growth & development
  • Semaphorin-3A
  • Tumor Suppressor Proteins
  • Ubiquitin / metabolism
  • Xenopus

Substances

  • Amanitins
  • Carrier Proteins
  • Cysteine Proteinase Inhibitors
  • Drosophila Proteins
  • Eukaryotic Initiation Factor-4E
  • Eye Proteins
  • Glycoproteins
  • Leupeptins
  • Lipopolysaccharides
  • Multienzyme Complexes
  • Nerve Growth Factors
  • Nucleic Acid Synthesis Inhibitors
  • Peptide Initiation Factors
  • Phosphoproteins
  • Semaphorin-3A
  • Tumor Suppressor Proteins
  • Ubiquitin
  • acetylleucyl-leucyl-norleucinal
  • Netrin-1
  • Phosphatidylinositol 3-Kinases
  • Receptor Protein-Tyrosine Kinases
  • tor protein, Drosophila
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex