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

Belkacem Otsmane1, Anice Moumen, Julianne Aebischer

  • 1The Mediterranean Institute of Neurobiology, Inmed, Marseille, France.

EMBO Reports
|March 27, 2014
PubMed

Insights

Tumor necrosis factor superfamily member LIGHT has dual roles in motoneurons. Somatic activation triggers death, while axonal stimulation promotes axon growth and branching, impacting nerve injury recovery.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Receptor-ligand interactions trigger diverse cellular activities.
  • The TNF family member LIGHT, via LT-βR, is known to induce motoneuron death.
  • Distinct cellular responses depend on receptor signaling pathways.

Purpose of the Study:

  • To investigate the dual role of LIGHT in motoneuron survival and axon regeneration.
  • To elucidate the signaling pathways and compartmentalization of LIGHT-induced responses.
  • To determine the role of LIGHT in functional recovery after peripheral nerve damage.

Main Methods:

  • Utilized motoneuron cultures and genetic manipulation (Light deletion).
  • Investigated signaling pathways including ERK and caspase-9.
  • Analyzed LIGHT expression in vivo following peripheral nerve injury.
  • Assessed functional recovery after nerve damage.

Main Results:

  • LIGHT promotes axon outgrowth and branching in motoneurons via LT-βR.
  • Axonal elongation and branching require ERK and caspase-9 pathways.
  • Somatic LIGHT activation induces cell death, whereas axonal stimulation promotes growth.
  • LIGHT expression increases at nerve injury sites, mediated by B lymphocytes.
  • Genetic deletion of Light significantly delays functional recovery.

Conclusions:

  • LIGHT exhibits context-dependent functions in motoneurons, promoting survival/growth or death.
  • Compartment-specific signaling dictates LIGHT's distinct cellular outcomes.
  • The LIGHT pathway is crucial for functional recovery following peripheral nerve injury.
  • Both central and peripheral LIGHT signaling contribute to motoneuron function.

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