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A divergent canonical WNT-signaling pathway regulates microtubule dynamics: Dishevelled signals locally to stabilize microtubules

Ciani, L; Krylova, O; Smalley, MJ; Dale, TC; Salinas, PC; (2004) A divergent canonical WNT-signaling pathway regulates microtubule dynamics: Dishevelled signals locally to stabilize microtubules. Journal of Cell Biology , 164 (2) pp. 243-253. 10.1083/jcb.200309096. Green open access

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Abstract

Dishevelled (DVL) is associated with axonal microtubules and regulates microtubule stability through the inhibition of the serine/threonine kinase, glycogen synthase kinase 3beta (GSK-3beta). In the canonical WNT pathway, the negative regulator Axin forms a complex with beta-catenin and GSK-3beta, resulting in beta-catenin degradation. Inhibition of GSK-3beta by DVL increases beta-catenin stability and TCF transcriptional activation. Here, we show that Axin associates with microtubules and unexpectedly stabilizes microtubules through DVL. In turn, DVL stabilizes microtubules by inhibiting GSK-3beta through a transcription- and beta-catenin-independent pathway. More importantly, axonal microtubules are stabilized after DVL localizes to axons. Increased microtubule stability is correlated with a decrease in GSK-3beta-mediated phosphorylation of MAP-1B. We propose a model in which Axin, through DVL, stabilizes microtubules by inhibiting a pool of GSK-3beta, resulting in local changes in the phosphorylation of cellular targets. Our data indicate a bifurcation in the so-called canonical WNT-signaling pathway to regulate microtubule stability.

Type: Article
Title: A divergent canonical WNT-signaling pathway regulates microtubule dynamics: Dishevelled signals locally to stabilize microtubules
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1083/jcb.200309096
Publisher version: http://dx.doi.org/10.1083/jcb.200309096
Language: English
Additional information: This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Cell Biology, beta-catenin, GSK-3 beta, neurons, cytoskeleton, axin, GLYCOGEN-SYNTHASE KINASE-3-BETA, BETA-CATENIN, TRANSCRIPTIONAL ACTIVATION, AXIN, PROTEIN, PHOSPHORYLATION, INHIBITION, LOCALIZATION, MECHANISMS, GENERATION
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10187489
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