Li, X., Roszko, I., Sepich, D.S., Ni, M., Hamm, H.E., Marlow, F.L., and Solnica-Krezel, L. (2013) Gpr125 modulates Dishevelled distribution and planar cell polarity signaling. Development (Cambridge, England). 140(14):3028-3039.
During vertebrate gastrulation, Wnt/planar cell polarity (PCP) signaling orchestrates polarized cell behaviors underlying
convergence and extension (C&E) movements to narrow embryonic tissues mediolaterally and lengthen them anteroposteriorly.
Here, we have identified Gpr125, an adhesion G protein-coupled receptor, as a novel modulator of the Wnt/PCP signaling system.
Excess Gpr125 impaired C&E movements and the underlying cell and molecular polarities. Reduced Gpr125 function exacerbated
the C&E and facial branchiomotor neuron (FBMN) migration defects of embryos with reduced Wnt/PCP signaling. At the molecular
level, Gpr125 recruited Dishevelled to the cell membrane, a prerequisite for Wnt/PCP activation. Moreover, Gpr125 and Dvl
mutually clustered one another to form discrete membrane subdomains, and the Gpr125 intracellular domain directly interacted
with Dvl in pull-down assays. Intriguingly, Dvl and Gpr125 were able to recruit a subset of PCP components into membrane subdomains,
suggesting that Gpr125 may modulate the composition of Wnt/PCP membrane complexes. Our study reveals a role for Gpr125 in
PCP-mediated processes and provides mechanistic insight into Wnt/PCP signaling.