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PMID:15207235
| Citation |
Zhou, FQ, Zhou, J, Dedhar, S, Wu, YH and Snider, WD (2004) NGF-induced axon growth is mediated by localized inactivation of GSK-3beta and functions of the microtubule plus end binding protein APC. Neuron 42:897-912 |
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| Abstract |
Little is known about how nerve growth factor (NGF) signaling controls the regulated assembly of microtubules that underlies axon growth. Here we demonstrate that a tightly regulated and localized activation of phosphatidylinositol 3-kinase (PI3K) at the growth cone is essential for rapid axon growth induced by NGF. This spatially activated PI3K signaling is conveyed downstream through a localized inactivation of glycogen synthase kinase 3beta (GSK-3beta). These two spatially coupled kinases control axon growth via regulation of a microtubule plus end binding protein, adenomatous polyposis coli (APC). Our results demonstrate that NGF signals are transduced to the axon cytoskeleton via activation of a conserved cell polarity signaling pathway. |
| Links |
PubMed Online version:10.1016/j.neuron.2004.05.011 |
| Keywords |
Adenomatous Polyposis Coli/metabolism; Analysis of Variance; Animals; Antineoplastic Agents/pharmacology; Axons/drug effects; Axons/physiology; Blotting, Western/methods; Cell Count; Cells, Cultured; Cytoskeletal Proteins/metabolism; Dose-Response Relationship, Drug; Drug Interactions; Embryo, Mammalian; Enzyme Inhibitors/pharmacology; Fluorescent Antibody Technique/methods; Ganglia, Spinal/cytology; Gene Expression Regulation/genetics; Gene Expression Regulation/physiology; Glycogen Synthase Kinase 3/metabolism; Green Fluorescent Proteins; Growth Cones/drug effects; Growth Cones/physiology; Luminescent Proteins/metabolism; Mice; Microtubule-Associated Proteins/metabolism; Microtubules/metabolism; Models, Neurological; Mutagenesis, Site-Directed/physiology; Nerve Growth Factors/immunology; Nerve Growth Factors/pharmacology; Nerve Growth Factors/physiology; Neurons/cytology; Neurons/drug effects; Neurons/physiology; Protein-Serine-Threonine Kinases/metabolism; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-akt; Signal Transduction/genetics; Signal Transduction/physiology; Trans-Activators/metabolism; Transfection/methods; Tubulin/metabolism; beta Catenin |
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Significance
Annotations
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