GDNF family ligands activate multiple events during axonal growth in mature sensory neurons.
The need for medical treatment of neuronal trauma motivates the search for new agents to stimulate posttraumatic axonal regrowth, as well as improving understanding of signaling cascades regulating this process. GDNF stimulates axonal regeneration in the peripheral nervous system, but little is known about the mechanism of this effect. Neurturin, artemin and persephin are homologs of GDNF, and their impact on axonal regeneration in adults has not been studied yet. Here we show that neurturin, artemin and GDNF, but not persephin, promote axonal initiation in cultured dorsal root ganglion neurons from young adult mice. This effect requires Src-family kinase activity as it was blocked by SU6656. In neurons from GFRalpha2-deficient mice, neurturin does not significantly promote axonal initiation. We also show that neurturin and GDNF induce extensive lamellipodia formation on neuronal somata and growth cones. GDNF, when applied after the time of axonal initiation in culture, also promotes axonal elongation.
Paveliev
Mikhail
M
Program for Molecular Neurobiology, Institute of Biotechnology, Viikki Biocenter, University of Helsinki, Helsinki FIN-00014, Finland.
Airaksinen
Matti S
MS
Saarma
Mart
M
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000494:pharmacology* / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000494:pharmacology* / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D051101:Neurturin; D011518:Proto-Oncogene Proteins / Q000819:agonists* / Q000172:deficiency / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics
C116599:Artn protein, mouse; C495040:Gdnf protein, mouse; C494991:Gfra2 protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D008024:Ligands; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D051101:Neurturin; C495056:Nrtn protein, mouse; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases