The Wnt signalling pathway is essential for development and the maintenance of stem cells. Here, the authors reveal how LGR4 and RSPO2 modulate ZNRF3 conformations and assembly heterogeneity, stabilising ZNRF3 in its inactive state to enhance Wnt signalling. These findings offer insights for the development of targeted therapies for Wnt-driven cancers.
- Lu Wang
- Fangzheng Hu
- Yong Geng