Neurotrophins rapidly modulate growth cone response to the axon guidance molecule, collapsin-1.
We show that neurotrophins acting at the growth cone via Trk receptors can mediate rapid and distinct changes in growth cone response to collapsin-1, an inhibitory axon guidance molecule. We find that the sensitivity of growth cones of dorsal root ganglia (DRG) neurons to collapsin-1 differs when chronically cultured in BDNF, NT-3, or NGF with those in BDNF most sensitive and those in NGF least sensitive. Further, growth cones chronically cultured in BDNF rapidly decrease their sensitivity to collapsin-1 with acute exposure to NGF. Conversely, growth cones chronically cultured in NGF rapidly increase their sensitivity to collapsin-1 with acute exposure to BDNF. These bidirectional effects of neurotrophins appear to be mediated by the neurotrophin-specific Trk receptors on the growth cones since most growth cones are immunopositive for TrkA and TrkB, the NGF and BDNF receptors, respectively, and k252a, a selective inhibitor of Trk-mediated responses to neurotrophins, diminishes collapsin-1-induced growth cone collapse. These findings indicate that the response of growth cones to axon guidance molecules is dynamic and can be rapidly and differentially modulated by neurotrophins.
Tuttle
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Molecular Neurobiology Laboratory, Salk Institute for Biological Sciences, La Jolla, California 92037, USA.
O'Leary
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D000818:Animals; D002478:Cells, Cultured; D002645:Chickens; D005727:Ganglia, Spinal / Q000254:growth & development / Q000502:physiology; D006023:Glycoproteins / Q000502:physiology*; D009414:Nerve Growth Factors / Q000502:physiology*; D017475:Receptors, Nerve Growth Factor / Q000502:physiology; D040121:Semaphorin-3A; D015398:Signal Transduction / Q000502:physiology
D006023:Glycoproteins; D009414:Nerve Growth Factors; D017475:Receptors, Nerve Growth Factor; D040121:Semaphorin-3A