Fas engagement induces neurite growth through ERK activation and p35 upregulation

Julie Desbarats1, Raymond B Birge, Manuelle Mimouni-Rongy

  • 1Department of Physiology, McGill University, Montréal, Quebec, Canada, H3G 1Y6. Julie@desbarats.mcgill.ca

Nature Cell Biology
|January 25, 2003
PubMed

Insights

Fas receptor engagement promotes neurite growth in sensory neurons by activating the ERK pathway. This signaling also accelerates nerve regeneration and functional recovery after injury in vivo.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Immunology

Background:

  • Fas (CD95) is a death receptor involved in apoptosis and growth signaling.
  • The role of Fas in neuronal growth and regeneration is not fully understood.

Purpose of the Study:

  • To investigate the role of Fas in primary sensory neuron growth and nerve regeneration.
  • To elucidate the molecular mechanisms underlying Fas-mediated neurite outgrowth.

Main Methods:

  • Crosslinking Fas on primary sensory neurons in vitro.
  • Analyzing the extracellular-signal regulated kinase (ERK) pathway activation and p35 upregulation.
  • Assessing sciatic nerve injury recovery in Fas-deficient (lpr) mice and with anti-Fas antibody treatment in vivo.

Main Results:

  • Fas crosslinking induced neurite growth via sustained ERK pathway activation and p35 upregulation.
  • Fas-deficient mice showed delayed functional recovery after sciatic nerve injury.
  • Administration of anti-Fas antibodies accelerated nerve regeneration and functional recovery.

Conclusions:

  • Fas acts as an inducer of neurite growth in primary sensory neurons.
  • Fas signaling contributes to nerve regeneration and functional recovery after injury in vivo.

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