A role of Dishevelled in relocating Axin to the plasma membrane during wingless signaling.
Wnt signaling causes changes in gene transcription that are pivotal for normal and malignant development. A key effector of the canonical Wnt pathway is beta-catenin, or Drosophila Armadillo. In the absence of Wnt ligand, beta-catenin is phosphorylated by the Axin complex, which earmarks it for rapid degradation by the ubiquitin system. Axin acts as a scaffold in this complex, to assemble beta-catenin substrate and kinases (casein kinase I [CKI] and glycogen synthase kinase 3 beta [GSK3]). The Adenomatous polyposis coli (APC) tumor suppressor also binds to the Axin complex, thereby promoting the degradation of beta-catenin. In Wnt signaling, this complex is inhibited; as a consequence, beta-catenin accumulates and binds to TCF proteins to stimulate the transcription of Wnt target genes. Wnt-induced inhibition of the Axin complex depends on Dishevelled (Dsh), a cytoplasmic protein that can bind to Axin, but the mechanism of this inhibition is not understood. Here, we show that Wingless signaling causes a striking relocation of Drosophila Axin from the cytoplasm to the plasma membrane. This relocation depends on Dsh. It may permit the subsequent inactivation of the Axin complex by Wingless signaling.
Cliffe
Adam
A
MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, United Kingdom.
Hamada
Fumihiko
F
Bienz
Mariann
M
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D060466:Axin Protein; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D000072261:Dishevelled Proteins; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D010750:Phosphoproteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015398:Signal Transduction; D051155:Wnt1 Protein
D048868:Adaptor Proteins, Signal Transducing; D060466:Axin Protein; C118000:Axn protein, Drosophila; D002352:Carrier Proteins; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; D008164:Luminescent Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D051155:Wnt1 Protein; C000606588:dsh protein, Drosophila; C074622:wg protein, Drosophila; D049452:Green Fluorescent Proteins