title: Co-localization of patched and activated sonic hedgehog to lysosomes in neurons.
abstract: We demonstrate co-localization of the Patched 1 (Ptc1) 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 immunoblot analysis revealed intracellular localization of native Ptc1 and ShhNT. Examination of the topological model of the Ptc1 receptor revealed a number of Yxxphi lysosomal targeting sequences consistent with our observations for Ptc1 sorting.
authors.affiliation: Department of Molecular and Cellular Biology, Ontario Cancer Institute, University Health Network, Toronto, Canada.
authors.forename: F G
authors.initials: FG
authors.lastname: Mastronardi
authors.forename: J
authors.initials: J
authors.lastname: Dimitroulakos
authors.forename: S
authors.initials: S
authors.lastname: Kamel-Reid
authors.forename: A S
authors.initials: AS
authors.lastname: Manoukian
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D053823:Hedgehog Proteins; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000378:metabolism; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011506:Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface; D013347:Subcellular Fractions / Q000378:metabolism; D014018:Tissue Distribution; D015534:Trans-Activators; D014407:Tumor Cells, Cultured
chemical_list: D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011506:Proteins; C000606240:Ptch1 protein, mouse; D011956:Receptors, Cell Surface; C509239:SHH protein, human; D015534:Trans-Activators