Somatic and axonal LIGHT signaling elicit degenerative and regenerative responses in motoneurons, respectively

EMBO Rep. 2014 May;15(5):540-7. doi: 10.1002/embr.201337948. Epub 2014 Mar 24.

Abstract

A receptor-ligand interaction can evoke a broad range of biological activities in different cell types depending on receptor identity and cell type-specific post-receptor signaling intermediates. Here, we show that the TNF family member LIGHT, known to act as a death-triggering factor in motoneurons through LT-βR, can also promote axon outgrowth and branching in motoneurons through the same receptor. LIGHT-induced axonal elongation and branching require ERK and caspase-9 pathways. This distinct response involves a compartment-specific activation of LIGHT signals, with somatic activation-inducing death, while axonal stimulation promotes axon elongation and branching in motoneurons. Following peripheral nerve damage, LIGHT increases at the lesion site through expression by invading B lymphocytes, and genetic deletion of Light significantly delays functional recovery. We propose that a central and peripheral activation of the LIGHT pathway elicits different functional responses in motoneurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / physiology*
  • B-Lymphocytes / immunology
  • Butadienes / pharmacology
  • Caspase 9 / metabolism
  • Caspase Inhibitors / pharmacology
  • Cell Proliferation
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Flavonoids / pharmacology
  • Lymphotoxin beta Receptor / antagonists & inhibitors
  • Lymphotoxin beta Receptor / metabolism
  • Mice
  • Mice, Knockout
  • Motor Neurons / metabolism*
  • Nitriles / pharmacology
  • Protein Kinase Inhibitors / pharmacology
  • Recombinant Proteins / genetics
  • Recombinant Proteins / pharmacology
  • Sciatic Nerve / injuries
  • Sciatic Nerve / pathology
  • Tumor Necrosis Factor Ligand Superfamily Member 14 / biosynthesis
  • Tumor Necrosis Factor Ligand Superfamily Member 14 / genetics*
  • Tumor Necrosis Factor Ligand Superfamily Member 14 / metabolism*

Substances

  • Butadienes
  • Caspase Inhibitors
  • Flavonoids
  • Lymphotoxin beta Receptor
  • Nitriles
  • Protein Kinase Inhibitors
  • Recombinant Proteins
  • Tnfsf14 protein, mouse
  • Tumor Necrosis Factor Ligand Superfamily Member 14
  • U 0126
  • Extracellular Signal-Regulated MAP Kinases
  • Caspase 9
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one