Hh-Np traffics to the plasma membrane

Stable Identifier
R-HSA-5362549
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
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Hh-Np traffics to the plasma membrane where it may cluster in lipid rafts. Cholesterol modification is thought to contribute to this transit and targeting, possibly by promoting interaction with the lipid raft components caveolin and flotillin2, although this has not been demonstrated in mammalian cells (reviewed in Gallet, 2011). Cholesterol and lipid modification also impact the effective signaling range of the secreted ligand: due to the hydrophobic nature of these modifications, Hh-Np remains closely associated with the plasma membrane of the secreting cell, where it is competent for short-range signaling to adjacent cells. Long-range signaling depends on a number of possible mechanisms to extract the ligand from the secreting cell, including oligomerization of ligand into micelle-like structures, cleavage of the C-terminal cholesterol moiety by metalloproteases, or interaction with additional factors that help promote release from the plasma membrane (reviewed in Gallet, 2011; Briscoe and Therond, 2013).

Literature References
PubMed ID Title Journal Year
23719536 The mechanisms of Hedgehog signalling and its roles in development and disease

Briscoe, J, Thérond, PP

Nat. Rev. Mol. Cell Biol. 2013
21257310 Hedgehog morphogen: from secretion to reception

Gallet, A

Trends Cell Biol. 2011
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