Fig. 5. Three models of how Fz and Dsh/Dvl may function in relation to Arrow/Lrp5/Lrp6-Axin interaction. In all three models, Wnt-induced Arrow/Lrp5/Lrp6 phopshorylation on the PPP(S/T)P motifs provides docking sites for Axin. (A) The co-recruitment model. Wnt-induced Fz-Lrp5/Lrp6 complex co-recruits Dvl and Axin into the co-receptor complex via Fz-Dvl and Lrp5/Lrp6-Axin interactions. This proximity of Dvl and Axin, which can interact with each other, causes functional inhibition or degradation of Axin by Dvl, either directly or via Dvl-associated proteins. (B) The vesicle transport model. Axin is shuttled to the plasma membrane to its docking sites in Arrow/Lrp5/Lrp6 via Dvl-mediated `vesicular-type' transport, which relies on the ability of Dvl to bind Axin and phospholipids/vesicles. In this and the above co-recruitment model, Dsh/Dvl is downstream of and required for Arrow/Lrp5/Lrp6 function. (C) The parallel signaling model. Fz-Dvl-Axin and Arrow/Lrp5/Lrp6-Axin are two parallel and independent branches. Activation of ß-catenin signaling requires both branches under physiological conditions, but can occur when either branch is overactivated, for example, following overexpression of Dvl or Arrow/Lrp5/Lrp6N. This model accounts for the possibility that Dsh/Dvl may not be required for overexpressed Arrow/Lrp5/Lrp6 to activate ß-catenin signaling.