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Secreted frizzled-related protein 2 (sFRP2) redirects non-canonical Wnt signaling from Fz7 to Ror2 during vertebrate gastrulation

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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 (sF...

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Main Authors: Brinkmann, Eva-Maria (Author) , Kumar, Rahul (Author) , Steinbeisser, Herbert (Author) , Kaufmann, Lilian (Author) , Özbek, Suat (Author)
Format: Article (Journal)
Language:English
Published: April 20, 2016
In: The journal of biological chemistry
Year: 2016, Volume: 291, Issue: 26, Pages: 13730-13742
ISSN:1083-351X
DOI:10.1074/jbc.M116.733766
Online Access:Verlag, Volltext: http://dx.doi.org/10.1074/jbc.M116.733766
Verlag, Volltext: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4919455/
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Author Notes:Eva-Maria Brinkmann, Benjamin Mattes, Rahul Kumar, Anja I. H. Hagemann, Dietmar Gradl, Steffen Scholpp, Herbert Steinbeisser, Lilian T. Kaufmann, and Suat Özbek
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Summary: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.
Item Description:Gesehen am 06.12.2018
Physical Description:Online Resource
ISSN:1083-351X
DOI:10.1074/jbc.M116.733766

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