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.
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A divergent canonical WNT-signaling pathway regulates microtubule dynamics dishevelled signals locally to stabilize microtub.pdf - Published Version Download (739kB) | Preview |
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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