APC Moonlights to Prevent Wnt Signalosome Assembly

Abstract

The scaffold protein APC has a well-known function in ensuring β-catenin destruction. In this issue of Developmental Cell, Saito-Diaz et al. (2018) uncover another role for APC in Wnt signaling: to prevent clathrin-dependent signalosome formation in the absence of ligand.

Figure 1

APC’s Two Means of Suppressing Wnt Signaling in the Absence of Ligand APC and APC2 are redundant in the destruction complex, which phosphorylates and targets β-catenin for degradation. Saito-Diaz et al. (2018) show that APC, but not APC2, has an additional function in preventing signalosome formation in the absence of Wnt ligand. In APC-depleted cells, APC2 cannot compensate for APC’s role in preventing clathrin-dependent signalosome formation. This leaves APC2 without a destruction complex to participate in. Thus, in the absence of APC, the signalosome forms, LRP6 is phosphorylated, and β-catenin is activated, along with downstream transcription.