Raf and akt mediate distinct aspects of sensory axon growth

Neuron. 2002 Jul 3;35(1):65-76. doi: 10.1016/s0896-6273(02)00752-3.

Abstract

Nerve growth factor (NGF) induces dramatic axon growth from responsive embryonic peripheral neurons. However, the roles of the various NGF-triggered signaling cascades in determining specific axon morphological features remain unknown. Here, we transfected activated and inhibitory mutants of Trk effectors into sensory neurons lacking the proapoptotic protein Bax. This allowed axon growth to be studied in the absence of NGF, enabling us to observe the contributions of individual signaling mediators. While Ras was both necessary and sufficient for NGF-stimulated axon growth, the Ras effectors Raf and Akt induced distinct morphologies. Activated Raf-1 caused axon lengthening comparable to NGF, while active Akt increased axon caliber and branching. Our results suggest that the different Trk effector pathways mediate distinct morphological aspects of developing neurons.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Size / genetics
  • Female
  • Fetus
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / embryology*
  • Ganglia, Spinal / metabolism*
  • Gene Expression / physiology
  • Growth Cones / metabolism*
  • Growth Cones / ultrastructure
  • MAP Kinase Kinase 1
  • Male
  • Mice
  • Mice, Knockout
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism
  • Nerve Growth Factor / metabolism
  • Neurons, Afferent / cytology
  • Neurons, Afferent / metabolism*
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins / deficiency*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins c-bcl-2*
  • Proto-Oncogene Proteins c-raf / deficiency*
  • Proto-Oncogene Proteins c-raf / genetics
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptor, trkA / genetics
  • Receptor, trkA / metabolism
  • Receptor, trkC / genetics
  • Receptor, trkC / metabolism
  • Signal Transduction / genetics
  • bcl-2-Associated X Protein
  • ras Proteins / genetics
  • ras Proteins / metabolism

Substances

  • Bax protein, mouse
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Nerve Growth Factor
  • Phosphatidylinositol 3-Kinases
  • Receptor Protein-Tyrosine Kinases
  • Receptor, trkA
  • Receptor, trkC
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins c-raf
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 1
  • Map2k1 protein, mouse
  • Mitogen-Activated Protein Kinase Kinases
  • ras Proteins