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PMID:14734535

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Citation

Ciani, L, Krylova, O, Smalley, MJ, Dale, TC and Salinas, PC (2004) A divergent canonical WNT-signaling pathway regulates microtubule dynamics: dishevelled signals locally to stabilize microtubules. J. Cell Biol. 164:243-53

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.

Links

PubMed PMC2172322 Online version:10.1083/jcb.200309096

Keywords

Adaptor Proteins, Signal Transducing; Animals; Animals, Newborn; COS Cells; Cell Line; Cercopithecus aethiops; Cerebellum/cytology; Glycogen Synthase Kinase 3/metabolism; Humans; Mice; Microtubules/physiology; Microtubules/ultrastructure; Neurons/cytology; Neurons/physiology; Phosphoproteins/physiology; Protein-Tyrosine Kinases/physiology; Proto-Oncogene Proteins/physiology; Signal Transduction; Transfection; Wnt Proteins

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:AXIN1

located_in

GO:0015630: microtubule cytoskeleton

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:DVL1

acts_upstream_of_or_within

GO:0001932: regulation of protein phosphorylation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1096327

P

Seeded From UniProt

complete

MOUSE:DVL1

located_in

GO:0015630: microtubule cytoskeleton

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:DVL1

located_in

GO:0030424: axon

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:DVL1

acts_upstream_of_or_within

GO:0007409: axonogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:AXIN1

acts_upstream_of_or_within

GO:0001932: regulation of protein phosphorylation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:94941

P

Seeded From UniProt

complete

MOUSE:AXIN1

acts_upstream_of_or_within

GO:0031122: cytoplasmic microtubule organization

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:94941

P

Seeded From UniProt

complete

MOUSE:AXIN1

colocalizes_with

GO:0005881: cytoplasmic microtubule

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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