Domains of Axin and Disheveled Required for Interaction and Function in Wnt Signaling

Disheveled blocks the degradation of β-catenin in response to Wnt signal by interacting with the scaffolding protein, Axin. To define this interaction in detail we undertook a mutational and binding analysis of the murine Axin and Disheveled proteins. The DIX domain of Axin was found to be important for association with Disheveled and two other regions of Axin (between residues 1–168 and 600–810) were identified that can promote the association of Axin and Disheveled. We found that the DIX domain of Disheveled is critical for association with Axin in vivo and for Disheveled activity. The Disheveled DIX domain controlled the ability of Disheveled to induce the accumulation of cytosolic β-catenin whereas the PDZ domain was not essential to this function.