JCB logo
PeproTech: Cell Culture Supplements
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 20 January 2004. doi:10.1083/jcb.200309096
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 164, Number 2, 243-253
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 721K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ciani, L.
Right arrow Articles by Salinas, P. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ciani, L.
Right arrow Articles by Salinas, P. C.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Article

A divergent canonical WNT-signaling pathway regulates microtubule dynamics

: Dishevelled signals locally to stabilize microtubules



Lorenza Ciani1, Olga Krylova1, Matthew J. Smalley2, Trevor C. Dale2, and Patricia C. Salinas1

1 Department of Biological Sciences, Imperial College London, London SW7 2AZ, England, UK
2 Centre for Cell and Molecular Biology, Institute of Cancer Research, London SW3 6JB, England, UK

Address correspondence to Patricia C. Salinas at her present address, Department of Anatomy and Developmental Biology, Rockefeller Building, University College London, University Street, London WC1E 6BT, England, UK. Tel: (44) 20-7679-6577. email: patricia.salinas{at}ucl.ac.uk

Dishevelled (DVL) is associated with axonal microtubules and regulates microtubule stability through the inhibition of the serine/threonine kinase, glycogen synthase kinase 3ß (GSK-3ß). In the canonical WNT pathway, the negative regulator Axin forms a complex with ß-catenin and GSK-3ß, resulting in ß-catenin degradation. Inhibition of GSK-3ß by DVL increases ß-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-3ß through a transcription- and ß-catenin–independent pathway. More importantly, axonal microtubules are stabilized after DVL localizes to axons. Increased microtubule stability is correlated with a decrease in GSK-3ß–mediated phosphorylation of MAP-1B. We propose a model in which Axin, through DVL, stabilizes microtubules by inhibiting a pool of GSK-3ß, 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.

Key Words: ß-catenin; GSK-3ß; neurons; cytoskeleton; axin

The online version of this article includes supplemental material.

L. Ciani's present address is Department of Anatomy and Developmental Biology, Rockefeller Building, University College London, University Street, London WC1E6BT, England, UK.

O. Krylova's present address is GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM195AW, England, UK.

T.C. Dale's present address is Cardiff School of Biosciences, Biomedical Sciences Building, Museum Avenue, Cardiff, CF10 3US, England, UK.

Abbreviations used in this paper: {Delta}PDZ-DVL, mouse DVL in which the PDZ site has been deleted; DVL, Dishevelled; DVL-ER, mouse DVL fused with the estrogen receptor; GSK-3ß, glycogen synthase kinase 3ß; NB2a, neuroblastoma 2a.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents