LRP6, a co-receptor for the morphogen Wnt, aids endocytosis of anthrax 
complexes. Here we report that Dickkopf1 (DKK1) protein, a secreted LRP6 ligand 
and antagonist, is also a modulator of anthrax toxin sensitivity. shRNA-mediated 
gene silencing or TALEN-mediated gene knockout of DKK1 reduced sensitivity of 
cells to PA-dependent hybrid toxins. However, unlike the solely inhibitory 
effect on Wnt signaling, the effects of DKK1 overexpression on anthrax toxicity 
were bidirectional, depending on its endogenous expression and cell context. 
Fluorescence microscopy and biochemical analyses showed that DKK1 facilitates 
internalization of anthrax toxins and their receptors, an event mediated by 
DKK1-LRP6-Kremen2 complex. Monoclonal antibodies against DKK1 provided 
dose-dependent protection to macrophages from killing by anthrax lethal toxin 
(LT). Our discovery that DKK1 forms ternary structure with LRP6 and Kremen2 in 
promoting PA-mediated toxin internalization provides a paradigm for bacterial 
exploitation of mechanisms that host cells use to internalize signaling 
proteins.