Microtubule stabilization specifies initial neuronal polarization.
Axon formation is the initial step in establishing neuronal polarity. We examine here the role of microtubule dynamics in neuronal polarization using hippocampal neurons in culture. We see increased microtubule stability along the shaft in a single neurite before axon formation and in the axon of morphologically polarized cells. Loss of polarity or formation of multiple axons after manipulation of neuronal polarity regulators, synapses of amphids defective (SAD) kinases, and glycogen synthase kinase-3beta correlates with characteristic changes in microtubule turnover. Consistently, changing the microtubule dynamics is sufficient to alter neuronal polarization. Application of low doses of the microtubule-destabilizing drug nocodazole selectively reduces the formation of future dendrites. Conversely, low doses of the microtubule-stabilizing drug taxol shift polymerizing microtubules from neurite shafts to process tips and lead to the formation of multiple axons. Finally, local stabilization of microtubules using a photoactivatable analogue of taxol induces axon formation from the activated area. Thus, local microtubule stabilization in one neurite is a physiological signal specifying neuronal polarization.
Witte
Harald
H
Axonal Growth and Regeneration, Max Planck Institute of Neurobiology, 82152 Martinsried, Germany.
Neukirchen
Dorothee
D
Bradke
Frank
F
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D016764:Cell Polarity / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000196:embryology* / Q000378:metabolism* / Q000648:ultrastructure; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006624:Hippocampus / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D016501:Neurites / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D015739:Nocodazole / Q000494:pharmacology; D017239:Paclitaxel / Q000031:analogs & derivatives; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D050257:Tubulin Modulators / Q000494:pharmacology
D036341:Intercellular Signaling Peptides and Proteins; D050257:Tubulin Modulators; C496826:Brsk1 protein, mouse; C496825:Brsk2 protein, mouse; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; C000605508:Gsk3b protein, rat; D017346:Protein Serine-Threonine Kinases; D038362:Glycogen Synthase Kinase 3; D017239:Paclitaxel; D015739:Nocodazole