The Dishevelled protein mediates several diverse biological processes. 
Intriguingly, within the same tissues where Xenopus Dishevelled (Xdsh) controls 
cell fate via canonical Wnt signaling, it also controls cell polarity via the 
vertebrate planar cell polarity (PCP) cascade [1, 2, 3, 4, 5, 6, 7, 8 and 9]. 
The relationship between subcellular localization of Dishevelled and its 
signaling activities remains unclear; conflicting results have been reported 
depending upon the organism and cell types examined [8, 9, 10, 11, 12, 13, 14, 
15, 16, 17, 18, 19 and 20]. We have approached this issue by developing new 
reagents to sequester wild-type Dishevelled protein either at the cell membrane 
or away from the cell membrane. Removal of Dishevelled from the cell membrane 
disrupts convergent extension by preventing Rho/Rac activation and mediolateral 
cell polarization. By manipulating the subcellular localization of K-->M (dsh1), 
we show that this mutation inhibits Dishevelled activation of Rac, regardless of 
its subcellular localization. These data demonstrate that membrane localization 
of Dishevelled is a prerequisite for vertebrate PCP signaling. However, both 
membrane-targeted and cytoplasm-targeted Dishevelled can potently activate 
canonical Wnt signaling, suggesting that local concentration of Dishevelled 
protein, but not its spatial localization, is central to canonical Wnt 
signaling. These results suggest that in vertebrate embryos, subcellular 
localization is insufficient to account for the pathway specificity of 
Dishevelled in the canonical Wnt versus PCP signaling cascades.