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J Biol Chem June 24, 2016; 291 (26): 13730-42.

Secreted Frizzled-related Protein 2 (sFRP2) Redirects Non-canonical Wnt Signaling from Fz7 to Ror2 during Vertebrate Gastrulation.

Brinkmann EM , Mattes B , Kumar R , Hagemann AI , Gradl D , Scholpp S , Steinbeisser H , Kaufmann LT , Özbek S .

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.

PubMed ID: 27129770
PMC ID: PMC4919455
Article link: J Biol Chem

Species referenced: Xenopus laevis
Genes referenced: frzb2 fzd7 gtf2i gtf2ird1 mapk8 myc pcdh8.2 ror2 sfrp1 sfrp2 szl tbxt wnt5a
Morpholinos: frzb2 MO1 fzd7 MO1 ror2 MO2 sfrp1 MO1 sfrp1 MO2 sfrp2 MO1

Phenotypes: Xla Wt + Hsa.sfrp2 (fig.1.a) [+]

Article Images: [+] show captions
References [+] :
Bhat, Structure-function analysis of secreted frizzled-related protein-1 for its Wnt antagonist function. 2007, Pubmed