Sonic Hedgehog Induces the Segregation of Patched and Smoothened in Endosomes

@article{Incardona2002SonicHI,
  title={Sonic Hedgehog Induces the Segregation of Patched and Smoothened in Endosomes},
  author={John P Incardona and Jean Gruenberg and Henk Roelink},
  journal={Current Biology},
  year={2002},
  volume={12},
  pages={983-995}
}
BACKGROUND Sonic hedgehog (Shh) signal transduction involves the ligand binding Patched1 (Ptc1) protein and a signaling component, Smoothened (Smo). A select group of compounds inhibits both Shh signaling, regulated by Ptc1, and late endosomal lipid sorting, regulated by the Ptc-related Niemann-Pick C1 (NPC1) protein. This suggests that Ptc1 regulates Smo activity through a common late endosomal sorting pathway also utilized by NPC1. During signaling, Ptc accumulates in endosomal compartments… Expand
Requirement of Smurf-mediated endocytosis of Patched1 in sonic hedgehog signal reception
TLDR
Endocytic sorting signals for the receptor Patched1 (Ptch1), comprising two ‘PPXY’ motifs, are reported that direct it to degradation in lysosomes that abolish the ability of Shh to sustain the proliferation of postnatal granule cell precursors in the cerebellum. Expand
Patched regulates Smoothened trafficking using lipoprotein-derived lipids
TLDR
Drosophila Ptc recruits internalized lipoproteins to Ptc-positive endosomes and that its sterol-sensing domain regulates trafficking of both lipids and Smo from this compartment, and it is proposed that Ptc normally regulates Smo degradation by changing the lipid composition of endosome through which Smo passes. Expand
Altered localization of Drosophila Smoothened protein activates Hedgehog signal transduction.
TLDR
Using Drosophila salivary gland cells in vivo and in vitro as a new assay for Hh signal transduction, the regulation of Hh-triggered Smo stabilization and relocalization is investigated. Expand
Patched1 and Patched2 inhibit Smoothened non-cell autonomously
TLDR
A model in which Ptch1/2 mediate secretion of a Smo-inhibitory cholesterol precursor is supported, in which cells with differing Ptch 1/2 status repressed the Hh response and Ptch2/2 mediates non-cell autonomous inhibition. Expand
Regulation of smoothened by Drosophila G-protein-coupled receptor kinases.
TLDR
The results suggest that Smo is regulated by distinct Ptc-dependent and Gprk2-dependent trafficking mechanisms in vivo, analogous to constitutive and activity-dependent regulation of GPCRs. Expand
Patched controls the Hedgehog gradient by endocytosis in a dynamin-dependent manner, but this internalization does not play a major role in signal transduction
TLDR
It is found that the ptc14 mutant does not block Hh spreading, as it has a failure in endocytosis, and this mutant protein is able to control the expression of Hh target genes as the wild-type protein, indicating that the internalization mediated by Ptc is not required for signal transduction. Expand
The Hedgehog Receptor Patched Is Involved in Cholesterol Transport
TLDR
It is suggested that Patched may contribute to cholesterol efflux from cells, and to modulation of the intracellular cholesterol concentration, which is an important step in Shh pathway activation. Expand
Mouse Rab23 regulates hedgehog signaling from smoothened to Gli proteins.
TLDR
It is demonstrated that Rab23 acts upstream of Gli transcription factors in patterning neural cell types in the spinal cord and appears to regulate subcellular localization of essential components of the Hedgehog pathway that act downstream of Smoothened and upstream ofGli proteins. Expand
Repression of Smoothened by Patched-Dependent (Pro-)Vitamin D3 Secretion
TLDR
Hh activates its signalling cascade by inhibiting Ptch1-dependent secretion of the 3β-hydroxysteroid (pro-)vitamin D3, which establishes Hh as a unique morphogen, because binding of Hh on one cell is capable of activating Hh-dependent signalling cascades on other cells. Expand
Role of Patched-1 Intracellular Domains in Canonical and Non-Canonical Hedgehog Signalling Events
TLDR
Patched-1 is the primary receptor for Hedgehog (Hh) ligands and mediates both canonical and non-canonical Hh signalling, and it is identified through co-immunoprecipitation that Ptch1 and c-src associate in an Hh-dependent manner, and that the Ptch 1 C-terminus regulates activation of c- src in response to Hh ligand. Expand
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TLDR
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TLDR
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TLDR
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