Dynein motors transport activated Trks to promote survival of target-dependent neurons

Nat Neurosci. 2004 Jun;7(6):596-604. doi: 10.1038/nn1242. Epub 2004 May 2.

Abstract

Mutations that alter dynein function are associated with neurodegenerative diseases, but it is not known why defects in dynein-dependent transport impair neuronal survival. Here we show that dynein function in axons is selectively required for the survival of neurons that depend on target-derived neurotrophins. Stimulation of axon terminals with neurotrophins causes internalization of neurotrophin receptors (Trks). Using real-time imaging of fluorescently tagged Trks, we show that dynein is required for rapid transport of internalized, activated receptors from axon terminals to remote cell bodies. When dynein-based transport is inhibited, neurotrophin stimulation of axon terminals does not support survival. These studies indicate that defects in dynein-based transport reduce trafficking of activated Trks and thereby obstruct the prosurvival effect of target-derived trophic factors, leading to degeneration of target-dependent neurons.

Publication types

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

MeSH terms

  • Animals
  • Axonal Transport / drug effects*
  • Axonal Transport / physiology
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cells, Cultured
  • Dyneins / antagonists & inhibitors
  • Dyneins / metabolism*
  • Female
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism
  • Nerve Growth Factors / pharmacology*
  • Neurons / drug effects*
  • Neurons / metabolism
  • Pregnancy
  • Rats
  • Receptors, Nerve Growth Factor / agonists
  • Receptors, Nerve Growth Factor / metabolism*

Substances

  • Nerve Growth Factors
  • Receptors, Nerve Growth Factor
  • Dyneins