title: Repulsive axon guidance by Draxin is mediated by protein Kinase B (Akt), glycogen synthase kinase-3β (GSK-3β) and microtubule-associated protein 1B.
abstract: Draxin is an important axon guidance cue necessary for the formation of forebrain commissures including the corpus callosum, but the molecular details of draxin signaling are unknown. To unravel how draxin signals are propagated we used murine cortical neurons and genetic and pharmacological approaches. We found that draxin-induced growth cone collapse critically depends on draxin receptors (deleted in colorectal cancer, DCC), inhibition of protein kinase B/Akt, activation of GSK-3β (glycogen synthase kinase-3β) and the presence of microtubule-associated protein MAP1B. This study, for the first time elucidates molecular events in draxin repulsion, links draxin and DCC to MAP1B and identifies a novel MAP1B-depenent GSK-3β pathway essential for chemo-repulsive axon guidance cue signaling.
authors.affiliation: Department of Biochemistry and Cell Biology, Max F. Perutz Laboratories (MFPL), University of Vienna, Vienna Biocenter (VBC), 1030, Vienna, Austria.
authors.forename: Rajeshwari
authors.initials: R
authors.lastname: Meli
authors.affiliation: Department of Biochemistry and Cell Biology, Max F. Perutz Laboratories (MFPL), University of Vienna, Vienna Biocenter (VBC), 1030, Vienna, Austria.
authors.forename: Petronela
authors.initials: P
authors.lastname: Weisová
authors.affiliation: Department of Biochemistry and Cell Biology, Max F. Perutz Laboratories (MFPL), University of Vienna, Vienna Biocenter (VBC), 1030, Vienna, Austria.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Propst
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D002478:Cells, Cultured; D000075389:DCC Receptor; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000172:deficiency / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009474:Neurons / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D000075389:DCC Receptor; C501910:Dcc protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; C534831:draxin protein, mouse; C085284:microtubule-associated protein 1B; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3