RT Journal Article
SR Electronic
T1 A divergent canonical WNT-signaling pathway regulates microtubule dynamics
JF The Journal of Cell Biology
JO J Cell Biol
FD Rockefeller University Press
SP 243
OP 253
DO 10.1083/jcb.200309096
VO 164
IS 2
A1 Ciani, Lorenza
A1 Krylova, Olga
A1 Smalley, Matthew J.
A1 Dale, Trevor C.
A1 Salinas, Patricia C.
YR 2004
UL http://jcb.rupress.org/content/164/2/243.abstract
AB Dishevelled (DVL) is associated with axonal microtubules and regulates microtubule stability through the inhibition of the serine/threonine kinase, glycogen synthase kinase 3β (GSK-3β). In the canonical WNT pathway, the negative regulator Axin forms a complex with β-catenin and GSK-3β, resulting in β-catenin degradation. Inhibition of GSK-3β by DVL increases β-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-3β through a transcription- and β-catenin–independent pathway. More importantly, axonal microtubules are stabilized after DVL localizes to axons. Increased microtubule stability is correlated with a decrease in GSK-3β–mediated phosphorylation of MAP-1B. We propose a model in which Axin, through DVL, stabilizes microtubules by inhibiting a pool of GSK-3β, 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.