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Release of Hh-Np from the secreting cell

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-5362798

PubChem

R-HSA-5362798

Description

Cholesterol and palmitoyl-modification of Hh-Np render the ligand highly hydrophobic and results in its close association with the plasma membrane of the producing cell after secretion. Hh-Np tethered in this way may cluster in sterol-rich lipid rafts where it is competent for short-range signaling. Cell surface Hh-Np also interacts with glypican components of the extracellular matrix and this interaction stabilizes the ligand and is required for its lateral spread. Together, clustering into lipid rafts and interaction with HSPGs may favour packaging of ligand into higher order forms required for ligand dispersal.
Long-range signaling requires release of Hh-Np from the secreting cell. Release is achieved through a number of possibly overlapping mechanisms. These include oligomerization into micelle-like structures, packaging into lipoprotein particles and interaction with cholesterol-binding adaptor proteins such as DISP and SCUBE2. In addition, Hh-Np can be released from the plasma membrane through proteolytic cleavage: NOTUM is a secreted enzyme that is thought to promote the release of Hh-Np by cleaving the GPI anchor of Hh-associated glypicans, while the transmembrane metalloprotease ADAM17 promotes long-range Hh signaling by removing the palmitoyl- and cholesterol-modified N- and C-termini of the membrane-associated ligand. How all these mechanisms are coordinated remains to be elucidated (reviewed in Briscoe and Therond, 2013; Gallet, 2011).

Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.

SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

Displaying **all 7** entries
UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
A7MBM2	Protein dispatched homolog 2	C15orf36 DISP2 DISPB KIAA1742 LINC00594	view
P78333	Glypican-5 [Cleaved into: Secreted glypican-5]	GPC5	view
P78536	Disintegrin and metalloproteinase domain-containing protein 17	ADAM17 ADAM18 CSVP TACE hCG_23065	view
Q14623	Indian hedgehog protein	IHH	view
Q15465	Sonic hedgehog protein	SHH	view
Q6P988	Palmitoleoyl-protein carboxylesterase NOTUM	NOTUM OK/SW-CL.30	view
Q9NQ36	Signal peptide, CUB and EGF-like domain-containing protein 2	CEGP1 SCUBE2	view

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