Figure 2.

Hedgehog processing and release. Hedgehog (HH) ligands are initially synthesized as inactive pro-peptides, which undergo internal cleavage and covalent modifications to attach cholesterol at the C-terminal end and palmitate at the N-terminal end. These dual-lipidated ligands are released from the cells by Dispatched (DISP) as multimers of HH themselves or as freely diffusing aggregates, with the help of SHUBE and SHEDDASE proteins. The ligands are also packaged into lipoprotein particles through their association with heparan sulfate proteoglycans (HSPGs) (adapted from J Dev Biol 2016; 4:23. Ramsbottom SA and Pownall ME. Regulation of hedgehog signaling inside and outside the cell (32)).