Raf and akt mediate distinct aspects of sensory axon growth.
Nerve growth factor (NGF) induces dramatic axon growth from responsive embryonic peripheral neurons. However, the roles of the various NGF-triggered signaling cascades in determining specific axon morphological features remain unknown. Here, we transfected activated and inhibitory mutants of Trk effectors into sensory neurons lacking the proapoptotic protein Bax. This allowed axon growth to be studied in the absence of NGF, enabling us to observe the contributions of individual signaling mediators. While Ras was both necessary and sufficient for NGF-stimulated axon growth, the Ras effectors Raf and Akt induced distinct morphologies. Activated Raf-1 caused axon lengthening comparable to NGF, while active Akt increased axon caliber and branching. Our results suggest that the different Trk effector pathways mediate distinct morphological aspects of developing neurons.
Neuroscience Center, University of North Carolina, 103 Mason Farm Road, Chapel Hill 27599, USA.
Annette
A
Markus
Jian
J
Zhong
William D
WD
Snider
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D048429:Cell Size / Q000235:genetics; D005260:Female; D005333:Fetus; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D048369:MAP Kinase Kinase 1; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2; D019908:Proto-Oncogene Proteins c-raf / Q000172:deficiency* / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D020917:Receptor, trkA / Q000235:genetics / Q000378:metabolism; D020812:Receptor, trkC / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D051028:bcl-2-Associated X Protein; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D020932:Nerve Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2; D019908:Proto-Oncogene Proteins c-raf; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; D020812:Receptor, trkC; D051028:bcl-2-Associated X Protein; D018631:ras Proteins; C494827:Bax protein, mouse; C482127:Map2k1 protein, mouse