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Publication : Microtubule stabilization specifies initial neuronal polarization.

First Author  Witte H Year  2008
Journal  J Cell Biol Volume  180
Issue  3 Pages  619-32
PubMed ID  18268107 Mgi Jnum  J:259126
Mgi Id  MGI:6148529 Doi  10.1083/jcb.200707042
Citation  Witte H, et al. (2008) Microtubule stabilization specifies initial neuronal polarization. J Cell Biol 180(3):619-32
abstractText  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.
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