Characterization of Potent Wnt/R-Spondin Agonist Proteins for Research and Therapeutic Applications

To overcome the challenge of purifying highly hydrophobic Wnt proteins in an active state, we have developed and characterized Wnt/R-Spondin agonist proteins that are designed to promote canonical Wnt signaling, without requiring Wnt protein. As shown in this application note, the Wnt/R-Spondin agonist proteins bind to Frizzled-7, LRP-5/6, and the R-Spondin receptor, Lgr5, and they display better activity in a Wnt/β-Catenin reporter assay than the Wnt-3a protein alone, and similar or better activity than Wnt-3a and the individual R-Spondin proteins together. Additionally, the Wnt/R-Spondin agonist proteins support robust intestinal organoid culture at lower concentrations than when the Wnt-3a and R-Spondin 1 proteins are added together.

Key Takeaways:

• The Wnt/R-Spondin agonist proteins are structurally unrelated to Wnt proteins, but they promote Wnt receptor activation and canonical Wnt signaling.
• The Wnt/R-Spondin agonist proteins bind to the Frizzled-7 Wnt receptor, the LRP-6 Wnt co-receptor, and the Lgr5, R-Spondin receptor.
• The Wnt/R-Spondin agonist proteins exhibit better activity than the Wnt-3a protein alone in a Wnt reporter assay, and either similar or better activity than Wnt-3a and the individual R-Spondin proteins together.
• The Wnt/R-Spondin agonist proteins support intestinal organoid culture at lower concentrations than when the Wnt-3a and R-Spondin 1 proteins are added together.

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