Destruction complex dynamics: Wnt/β-catenin signaling alters Axin-GSK3β interactions in<i>in vivo</i>

Abstract

The central regulator of the Wnt/β-catenin pathway is the Axin/APC/GSK3β destruction complex (DC), which, under unstimulated conditions, targets cytoplasmic β-catenin for degradation. How Wnt activation inhibits the DC to permit β-catenin-dependent signaling remains controversial, in part because the DC and its regulation have never been observed <i>in vivo</i> Using bimolecular fluorescence complementation (BiFC) methods, we have now analyzed the activity of the DC under near-physiological conditions in <i>Drosophila</i> By focusing on well-established patterns of Wnt/Wg signaling in the developing <i>Drosophila</i> wing, we have defined the sequence of events by which activated Wnt receptors induce a conformational change within the DC, resulting in modified Axin-GSK3β interactions that prevent β-catenin degradation. Surprisingly, the nucleus is surrounded by active DCs, which principally control the degradation of β-catenin and thereby nuclear access. These DCs are inactivated and removed upon Wnt signal transduction. These results suggest a novel mechanistic model for dynamic Wnt signal transduction <i>in vivo</i>.