Spatially and functionally distinct roles of the PI3-K effector pathway during NGF signaling in sympathetic neurons

Neuron. 2000 Sep;27(3):499-512. doi: 10.1016/s0896-6273(00)00061-1.

Abstract

NGF is a target-derived growth factor for developing sympathetic neurons. Here, we show that application of NGF exclusively to distal axons of sympathetic neurons leads to an increase in PI3-K signaling in both distal axons and cell bodies. In addition, there is a more critical dependence on PI3-K for survival of neurons supported by NGF acting exclusively on distal axons as compared to neurons supported by NGF acting directly on cell bodies. Interestingly, PI3-K signaling within both cell bodies and distal axons contributes to survival of neurons. The requirement for PI3-K signaling in distal axons for survival may be explained by the finding that inhibition of PI3-K in the distal axons attenuates retrograde signaling. Therefore, a single TrkA effector, PI3-K, has multiple roles within spatially distinct cellular locales during retrograde NGF signaling.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Axonal Transport / drug effects
  • Axons / drug effects
  • Axons / metabolism
  • Cell Compartmentation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Nerve Growth Factor / metabolism*
  • Nerve Growth Factor / pharmacology
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins*
  • Rats
  • Receptor, trkA / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Sympathetic Nervous System / cytology
  • Sympathetic Nervous System / metabolism*

Substances

  • Proto-Oncogene Proteins
  • Nerve Growth Factor
  • Phosphatidylinositol 3-Kinases
  • Receptor, trkA
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt