A Role of Dishevelled in Relocating Axin to the Plasma Membrane during Wingless Signaling
Abstract
Wnt signaling causes changes in gene transcription that are pivotal for normal and malignant development [1, 2]. A key effector of the canonical Wnt pathway is β-catenin, or Drosophila Armadillo. In the absence of Wnt ligand, β-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 β-catenin substrate and kinases (casein kinase I [CKI] and glycogen synthase kinase 3β [GSK3]) [3, 4]. The Adenomatous polyposis coli (APC) tumor suppressor also binds to the Axin complex, thereby promoting the degradation of β-catenin [5, 6]. In Wnt signaling, this complex is inhibited; as a consequence, β-catenin accumulates and binds to TCF proteins to stimulate the transcription of Wnt 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.
- Publication:
-
Current Biology
- Pub Date:
- May 2003
- DOI:
- 10.1016/S0960-9822(03)00370-1
- Bibcode:
- 2003CBio...13..960C