Soluble and bound forms of GFRalpha1 elicit different GDNF-independent neurite growth responses in primary sensory neurons.
We have investigated the role of glial cell-line derived neurotrophic factor (GDNF) and the effect of soluble or immobilized localization of its GDNF family receptor alpha1 (GFRalpha1) on neurite growth in cultured embryonic Bax(-/-) dorsal root ganglion neurons, which survive in the absence of trophic support. Whereas GDNF alone has a moderate effect on neurite growth, soluble and immobilized GFRalpha1 elicit opposing and GDNF-independent effects on neurite growth by a phospholipase C (PLC) gamma-dependent mechanism. Thus, GFRalpha1 elicits nerve growth responses independent of GDNF. However, GDNF in the presence of soluble or immobilized GFRalpha1 reverse the GDNF-independent GFRalpha1 modulation of neurite growth. The different outcome of soluble and bound GFRalpha1 combined with our previous immunohistochemical data showing GFRalpha1-protein in Schwann cells but not axons suggest terminal Schwann cells as a source of locally administered target-derived GFRalpha1 and place this receptor in the path of axonal growth and guidance. Thus, target-derived GFRalpha1 play opposing roles when presented alone and with GDNF and, therefore, can function as a nerve growth cue that both can promote and prevent growth in the developing peripheral nervous system.
Mikaels-Edman
Asa
A
Laboratory of Molecular Neurobiology, MBB, Karolinska Institute, Stockholm, Sweden.
Baudet
Christel
C
Ernfors
Patrik
P
D000818:Animals; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D051379:Mice; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000378:metabolism*; D009475:Neurons, Afferent / Q000166:cytology / Q000502:physiology*; D051966:Phospholipase C gamma; D010742:Phospholipid Ethers / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D004791:Enzyme Inhibitors; C495040:Gdnf protein, mouse; C494988:Gfra1 protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D009414:Nerve Growth Factors; D010742:Phospholipid Ethers; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C026659:edelfosine; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma