Which of the following defines the role of R-spondin in Wnt signaling?
R-spondins 1-4 are cysteine-rich secreted potentiators containing furin and thrombospondin domains amplifying Wnt responses dramatically. They simultaneously bind leucine-rich repeat GPCRs LGR4, LGR5, LGR6 marking stem cells and transmembrane E3 ubiquitin ligases ZNRF3, RNF43 which normally ubiquitinate Frizzled for lysosomal degradation reducing surface receptor availability. R-spondin-LGR complex internalizes and inhibits ZNRF3/RNF43, stabilizing Frizzled receptors increasing membrane availability and amplifying Wnt/beta-catenin signaling several hundred-fold. This sustains intestinal crypt,
Ref: de Lau et al., Genes & Development 2014: R-spondin binds LGR and ZNRF3 to stabilize Frizzled and amplify Wnt.
