Fig. 2.

Schematic diagram of Rspo-induced Wnt signaling augmentation. Without Rspos, Frizzled is ubiquitinated by Znrf3/Rnf43 followed by endocytosis of receptor complex and initiation of Wnt signaling is inhibited. Rspos bind to their receptors Lgr4/5/6 and this complex bind to Znrf3/Rnf43 followed by membrane clearance of these E3 ubiquitin ligases. This allows the receptor complex to initiate downstream signaling, which in turn leads to augmentation of Wnt signaling cascade. Importantly, Rspo2/3 are currently proposed to accelerate Wnt signaling through Lgr-independent signaling.