TY  - GEN
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/20159/
A1  - Brinkmann, Eva-Maria
N2  - Proper cell movements require balanced activities of different signaling cascades, but factors regulating this interplay on the molecular level are poorly characterized.
During embryogenesis, convergent extension (CE) movements are mainly regulated by three branches of non-canonical Wnt signaling: Ror2 mediated signaling, Frizzled mediated classical Wnt/PCP signaling, and the Wnt/Ca2+ signaling pathway.Secreted frizzled-related proteins (sFRPs) are known as inhibitors or biphasic modulators of Wnt/ß-catenin signaling but less is known about their function in ß-catenin independent Wnt pathways.
Here, I show that secreted frizzled-related protein 2 (sFRP2), a member of the sFRP family, is required for morphogenesis and papc expression during Xenopus
gastrulation. Notably, sFRP2 redirects non-canonical Wnt signaling from Fz7 to Ror2. During this process, sFRP2 promotes Ror2 signal transduction by stabilizing
Wnt5a/Ror2 complexes at the membrane while it inhibits Fz7 signaling, probably by blocking Fz7 receptor endocytosis.
Direct interaction of the two receptors via their CRDs also promotes Ror2 mediated papc expression but inhibits Fz7 signaling. Furthermore, other Fz-CRD containing
proteins, such as other sFRP1 and frzb2 can also mediate this function. While the cysteine-rich domain (CRD) of sFRP2 is sufficient for Ror2 activation, the NTR
domain of sFRP2 seems to be important for efficient Fz7 inhibition since the CRD alone could not prevent Fz7 receptor internalization.
Based on my results, I propose that sFRPs act as a molecular switch channeling the signal input for different non-canonical Wnt pathways during vertebrate gastrulation.
ID  - heidok20159
Y1  - 2016///
TI  - Secreted frizzled-related protein 2 (sFRP2) redirects non-canonical Wnt signaling from Fz7 to Ror2 during vertebrate gastrulation
AV  - public
ER  -