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

• Verfasst von: Brinkmann, Eva-Maria [VerfasserIn]
• Verfasst von: Kumar, Rahul [VerfasserIn]
• Verfasst von: Steinbeisser, Herbert [VerfasserIn]
• Verfasst von: Kaufmann, Lilian [VerfasserIn]
• Verfasst von: Özbek, Suat [VerfasserIn]
• Titel: Secreted frizzled-related protein 2 (sFRP2) redirects non-canonical Wnt signaling from Fz7 to Ror2 during vertebrate gastrulation
• Verf.angabe: Eva-Maria Brinkmann, Benjamin Mattes, Rahul Kumar, Anja I. H. Hagemann, Dietmar Gradl, Steffen Scholpp, Herbert Steinbeisser, Lilian T. Kaufmann, and Suat Özbek
• E-Jahr: 2016
• Jahr: April 20, 2016
• Umfang: 13 S.
• Fussnoten: Gesehen am 06.12.2018
• Titel Quelle: Enthalten in: The journal of biological chemistry
• Ort Quelle: Bethesda, Md. : ASBMB Publications, 1905
• Jahr Quelle: 2016
• Band/Heft Quelle: 291(2016), 26, Seite 13730-13742
• ISSN Quelle: 1083-351X
• DOI: doi:10.1074/jbc.M116.733766
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1584913134

Abstract

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.