title: NGF-induced axon growth is mediated by localized inactivation of GSK-3beta and functions of the microtubule plus end binding protein APC.
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.
authors.affiliation: UNC-Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Feng-Quan
authors.initials: FQ
authors.lastname: Zhou
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhou
authors.forename: Shoukat
authors.initials: S
authors.lastname: Dedhar
authors.forename: Yao-Hong
authors.initials: YH
authors.lastname: Wu
authors.forename: William D
authors.initials: WD
authors.lastname: Snider
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western / Q000379:methods; D002452:Cell Count; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique / Q000379:methods; D005727:Ganglia, Spinal / Q000166:cytology; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D049452:Green Fluorescent Proteins; D020439:Growth Cones / Q000187:drug effects / Q000502:physiology; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D008959:Models, Neurological; D016297:Mutagenesis, Site-Directed / Q000502:physiology; D009414:Nerve Growth Factors / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism; D014162:Transfection / Q000379:methods; D014404:Tubulin / Q000378:metabolism; D051176:beta Catenin
chemical_list: D000970:Antineoplastic Agents; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; C405804:EB1 microtubule binding proteins; D004791:Enzyme Inhibitors; D008164:Luminescent Proteins; D008869:Microtubule-Associated Proteins; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014404:Tubulin; D051176:beta Catenin; D049452:Green Fluorescent Proteins; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3