Domains of Axin and disheveled required for interaction and function in Wnt signaling

Disheveled blocks the degradation of beta-catenin in response to Wnt signal by interacting with the scaffolding protein, Axin. To define this interact ion 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 import ant for association with Disheveled and two other regions of Axin (between residues 1-168 and 600-810) mere identified that can promote the associatio n of Axin and Disheveled. We found that the DM domain of Disheveled is crit ical for association with Axin in vivo and for Disheveled activity. The Dis heveled DIX domain controlled the ability of Disheveled to induce the accum ulation of cytosolic beta-catenin whereas the PDZ domain was not essential to this function. (C) 2000 Academic Press.