Xenopus frizzled-4S, a splicing variant of Xfz4 is a context-dependent activator and inhibitor of Wnt/β-catenin signaling

摘要: Background: Secreted Frizzled related proteins (SFRPs) are extracellular regulators of Wnt signaling. These contain an N-terminal cysteine rich domain (CRD) highly similar to the CRDs family seven-transmembrane that act as receptors. SFRPs can bind Wnts and prevent their interaction with receptor. Recently it has been reported a splice variant human Frizzled-4 (FZD4S) lacking transmembrane cytoplasmic domains activate rather than inhibit Wnt-8 activity in Xenopus embryos. This indicates secreted CRD containing such ecto-domains may not always inhibitors. It is known how FZD4S Wnt/βcatenin signaling what biological role this molecule plays vivo. Results: Here we report frizzled-4 alternatively spliced give rise putative protein lacks domains. We performed functional experiments embryos investigate novel splicing variant, Xfz4S, modulate Wnt/β-catenin pathway. show Xfz4S well Xfz8 (ECD8) both activators inhibitors dependent on ligand presented. The positive regulation by receptors mediated members low density lipoprotein receptorrelated (LRP-5/6) coreceptors. Conclusion: work provides evidence