FIGURE 7:

Model for the function of Wdp in modulating Hh signaling. The seven-pass transmembrane protein Smo is a key transducer of Hh signaling. In the absence of Hh, Ptc keeps Smo in intracellular vesicles. Hh inhibits the activity of Ptc, allowing Smo to translocate to the plasma membrane and activate downstream signaling. Our preliminary study shows that wdp RNAi knockdown increases the level of Smo protein (data not shown). Given that Wdp negatively regulates JAK–STAT signaling by promoting the degradation of the Dome receptor (Ren et al., 2015), it may down-regulate Hh signaling via a similar mechanism: reducing Smo protein levels. However, the molecular mechanism of Wdp activity in Hh signaling remains elusive.