Co-localization of Patched and activated Sonic hedgehog to lysosomes in neurons

We demonstrate co-localization of the Patched 1 (Ptcl) receptor and its ligand sonic hedgehog (Shh) in lysosomes suggests an intracellular sorting mechanism for this receptor and its ligand. Treatment of murine brain primary cultures and a human teratoma cell line with the N-terminal activated form of Shh (ShhNT), a Ptc1-Shh complex was observed in lysosomes. Consistent with this interaction, Western immuno-blot analysis revealed intracellular localization of native Ptc1 and ShhNT. Examination of the topological model of the Ptc1 receptor revealed a number of Yxx lysosomal targeting sequences consistent with our observations for Ptc1 sorting.