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(A) ZNRF3 promotes turnover of FZ and LRP6 via acting as a ubiquitin ligase. (B) Rspo binds to both ZNRF3 and LGR4, which promotes ZNRF3 turnover likely through its autoubiquitination, thereby stabilizing FZ and LRP6 for a greater Wnt response. Whether LGR4 has additional signaling function in the FZ-LRP6 complex is unknown. Rspo stabilization of FZ also enhances Wnt/PCP signaling (not depicted).
