Figure 2. Hedgehog secretion and endocytosis.

Fully processed Shh is trafficked from the Golgi into acidified vesicles where they are complexed into multimers by the proton driven pump activity of Disp1. The complexes are subsequently released in the extracellular space, and subsequently bound and internalized by the action of Ptch1 in adjacent cells. Trafficking of the complex to late endosomes exposes Ptch1 to a lower pH, which is required for the activation of the downstream pathway components.