Axonal elongation triggered by stimulus-induced local translation of a polarity complex protein

Nat Cell Biol. 2009 Aug;11(8):1024-30. doi: 10.1038/ncb1916. Epub 2009 Jul 20.

Abstract

During development, axon growth rates are precisely regulated to provide temporal control over pathfinding. The precise temporal regulation of axonal growth is a key step in the formation of functional synapses and the proper patterning of the nervous system. The rate of axonal elongation is increased by factors such as netrin-1 and nerve growth factor (NGF), which stimulate axon outgrowth using incompletely defined pathways. To clarify the mechanism of netrin-1- and NGF-stimulated axon growth, we explored the role of local protein translation. We found that intra-axonal protein translation is required for stimulated, but not basal, axon outgrowth. To identify the mechanism of translation-dependent outgrowth, we examined the PAR complex, a cytoskeleton regulator. We found that the PAR complex, like local translation, is required for stimulated, but not basal, outgrowth. Par3 mRNA is localized to developing axons, and NGF and netrin-1 trigger its local translation. Selective ablation of Par3 mRNA from axons abolishes the outgrowth-promoting effect of NGF. These results identify a new role for local translation and the PAR complex in axonal outgrowth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Axons / drug effects*
  • Axons / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Culture Techniques / instrumentation
  • Cell Polarity
  • Cells, Cultured
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / embryology
  • Gene Expression / drug effects
  • In Situ Hybridization, Fluorescence
  • Microscopy, Fluorescence
  • Nerve Growth Factor / pharmacology*
  • Nerve Growth Factors / pharmacology*
  • Nerve Tissue Proteins
  • Netrin-1
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism
  • Protein Binding
  • Protein Biosynthesis / drug effects*
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism
  • RNA Interference
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Tumor Suppressor Proteins / pharmacology*

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Ntn1 protein, rat
  • Pard3 protein, rat
  • Pard6a protein, rat
  • Tumor Suppressor Proteins
  • Netrin-1
  • Nerve Growth Factor
  • PKC-3 protein
  • Protein Kinase C