A role of dishevelled in relocating axin to the plasma membrane during wingless signaling

Writ signaling causes changes in gene transcription that are pivotal for normal and malignant development [1, 2]. A key effector of the canonical Writ pathway is beta-catenin, or Drosophila Armadillo. In the absence of Writ 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 3P [GSK3]) [3, 4]. The Adenomatous polyposis coli (APC) tumor suppressor also binds to the Axin complex, thereby promoting the degradation of beta-catenin [5, 6]. In Writ signaling, this complex is inhibited; as a consequence, beta-catenin accumulates and binds to TCF proteins to stimulate the transcription of Writ target genes [1, 2]. Wnt-induced inhibition of the Axin complex depends on Dishevelled (Dsh) [7-9], a cytoplasmic protein that can bind to Axin [10, 11], 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.