Frizzled
The Frizzled Extracellular Domain Is a Ligand for Van Gogh/Stbm during Nonautonomous Planar Cell Polarity Signaling
15/09/2008
The Frizzled (Fz) receptor is required cell
autonomously in Wnt/β-catenin and planar cell
polarity (PCP) signaling. In addition to these
requirements, Fz acts nonautonomously during PCP
establishment: wild-type cells surrounding fz−
patches reorient toward the fz− cells. The molecular
mechanism(s) of nonautonomous Fz signaling are
unknown. Our in vivo studies identify the
extracellular domain (ECD) of Fz, in particular its
CRD (cysteine rich domain), as critical for
nonautonomous Fz-PCP activity. Importantly, we
demonstrate biochemical and physical interactions
between the FzECD and the transmembrane protein Van
Gogh/Strabismus (Vang/Stbm). We show that this
function precedes cell-autonomous interactions and
visible asymmetric PCP factor localization. Our data
suggest that Vang/Stbm can act as a FzECD receptor,
allowing cells to sense Fz activity/levels of their
neighbors. Thus, direct Fz-Vang/Stbm interactions
represent an intriguing mechanism that may account
for the global orientation of cells within the plane
of their epithelial field.
Developmental Cell, Vol 15, 462-469, 16 September 2008
Developmental Cell, Vol 15, 462-469, 16 September 2008
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