Fas engagement induces neurite growth through ERK activation and p35 upregulation.
Fas (also known as CD95), a member of the tumour-necrosis receptor factor family of 'death receptors', can induce apoptosis or, conversely, can deliver growth stimulatory signals. Here we report that crosslinking Fas on primary sensory neurons induces neurite growth through sustained activation of the extracellular-signal regulated kinase (ERK) pathway and the consequent upregulation of p35, a mediator of neurite outgrowth. In addition, functional recovery after sciatic nerve injury is delayed in Fas-deficient lpr mice and accelerated by local administration of antibodies against Fas, which indicates that Fas engagement may contribute to nerve regeneration in vivo. Our findings define a role for Fas as an inducer of both neurite growth in vitro and accelerated recovery after nerve injury in vivo.
Desbarats
Julie
J
Department of Physiology, McGill University, Montréal, Quebec, Canada, H3G 1Y6. Julie@desbarats.mcgill.ca
Birge
Raymond B
RB
Mimouni-Rongy
Manuelle
M
Weinstein
David E
DE
Palerme
Jean-Sébastien
JS
Newell
M Karen
MK
D000818:Animals; D046508:Culture Techniques; D004789:Enzyme Activation; D005434:Flow Cytometry; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology; D006801:Humans; D008124:Locomotion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D012584:Sciatic Nerve / Q000293:injuries / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000502:physiology*; D019014:fas Receptor / Q000378:metabolism*
D009419:Nerve Tissue Proteins; D019014:fas Receptor; C089495:neuronal Cdk5 activator (p25-p35); D020928:Mitogen-Activated Protein Kinases