Figure 7: A proposed model for Daple-mediated regulation of Rac activation and lamellipodia formation.

(a) In cells cultured in nutrient-rich medium (one containing 10% FBS), Daple overexpression facilitates the interaction of Dvl with PKCλ at the leading edge, which results in the activation of Rac and lamellipodia formation. Although speculative at present, it is conceivable that the Dvl/PKCλ protein complex regulates Rac activity through Rac-specific guanine nucleotide-exchange factors (GEFs), such as STEF/Tiam1. It is possible that the serum contains Wnt ligands or alternative external stimuli to promote the function of Daple (left panel). Conversely, Daple depletion attenuates the Dvl/PKCλ complex, leading to the decrease of basal Rac activation (right panel). (b) In cells cultured in nutrient-limited medium or those after serum withdrawal, Wnt5a stimulation induces clathrin-mediated internalisation of the Fz receptor, which signals by recruiting Dvl. Upon Wnt5a stimulation, Daple mediates the formation of the Dvl/PKCλ protein complex, leading to Rac activation and lamellipodia formation (upper panels). Conversely, in Daple-depleted cells, because of the impairment of Dvl/PKCλ interaction, cells fail to activate Rac and form lamellipodia even in the presence of Wnt5a (lower panels).