Secreted Frizzled-related Protein 2 (sFRP2) Redirects Non-canonical Wnt Signaling from Fz7 to Ror2 during Vertebrate Gastrulation
Journal of Biological Chemistry
American Society for Biochemistry and Molecular Biology
Convergent extension movements during vertebrate gastrulation require a balanced activity of non-canonical Wnt signaling pathways, but the factors regulating this interplay on the molecular level are poorly characterized. Here we show that sFRP2, a member of the secreted frizzled-related protein (sFRP) family, is required for morphogenesis and papc expression during Xenopus gastrulation. We further provide evidence that sFRP2 redirects non-canonical Wnt signaling from Frizzled 7 (Fz7) to the receptor tyrosine kinase-like orphan receptor 2 (Ror2). During this process, sFRP2 promotes Ror2 signal transduction by stabilizing Wnt5a-Ror2 complexes at the membrane, whereas it inhibits Fz7 signaling, probably by blocking Fz7 receptor endocytosis. The cysteine-rich domain of sFRP2 is sufficient for Ror2 activation, and related sFRPs can substitute for this function. Notably, direct interaction of the two receptors via their cysteine-rich domains also promotes Ror2-mediated papc expression but inhibits Fz7 signaling. We propose that sFRPs can act as a molecular switch, channeling the signal input for different non-canonical Wnt pathways during vertebrate gastrulation.
This is the final version of the article. Available from American Society for Biochemistry and Molecular Biology via the DOI in this record.
Vol. 291 (26), pp. 13730 - 13742
Place of publication
Showing items related by title, author, creator and subject.
Zhang, J; Fan, F; Zhao, Y; Sun, L; Liu, Y; Keegan, RM; Isupov, MN; Wu, Y (International Union of Crystallography, 2017-02-28)Helicobacter pylori, a Gram-negative bacterial pathogen prevalent in the human population, is the causative agent of severe gastric diseases. An H. pylori type IV secretion (T4S) system encoded by the cytotoxin-associated ...
Deciphering Developmental Disorders Study (Springer Nature, 2017-01-25)The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing ...
Australin: a chromosomal passenger protein required specifically for Drosophila melanogaster male meiosis. Gao, S; Giansanti, MG; Buttrick, GJ; Ramasubramanyan, S; Auton, A; Gatti, M; Wakefield, JG (Rockefeller University Press, 2008-02-11)The chromosomal passenger complex (CPC), which is composed of conserved proteins aurora B, inner centromere protein (INCENP), survivin, and Borealin/DASRA, localizes to chromatin, kinetochores, microtubules, and the cell ...