Reactome | GPR161 is internalized

GPR161 is internalized

Stable Identifier

R-HSA-5635102

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

ciliary membrane, endocytic vesicle membrane

ReviewStatus

5/5

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Hh signaling promotes the removal of the orphan G protein coupled receptor GPR161 from the cilium (Rohatgi et al, 2007). GPR161 is a negative regulator of Hh signaling that is recruited to the cilium through interaction with TULP3 (Mukhopadhyay et al, 2010; Mukhopadhyay et al, 2013). GPR161 thought to act by locally increasing the cAMP levels, promoting PKA activity and thereby favouring the production of the repressor form of the GLI proteins in the absence of Hh ligand. Consistent with this, deletion of GPR161 results in ectopic pathway activation (Mukhopadhyay et al, 2013). The decrease in PKA activity in the cilium after clearance of GPR161 from the ciliary membrane may contribute to the dissociation of the GLI:SUFU complex upon pathway activation, although this remains to formally demonstrated (Humke et al, 2010; Tukachinsky et al, 2010; reviewed in Mukhopadhyay et al, 2014).

Literature References

PubMed ID	Title	Journal	Year
23332756	The ciliary G-protein-coupled receptor Gpr161 negatively regulates the Sonic hedgehog pathway via cAMP signaling Mukhopadhyay, S, Wen, X, Ratti, N, Loktev, A, Rangell, L, Scales, SJ, Jackson, PK	Cell	2013
20889716	TULP3 bridges the IFT-A complex and membrane phosphoinositides to promote trafficking of G protein-coupled receptors into primary cilia Mukhopadhyay, S, Wen, X, Chih, B, Nelson, CD, Lane, WS, Scales, SJ, Jackson, PK	Genes Dev.	2010
20360384	The output of Hedgehog signaling is controlled by the dynamic association between Suppressor of Fused and the Gli proteins Humke, EW, Dorn, KV, Milenkovic, L, Scott, MP, Rohatgi, R	Genes Dev.	2010
20956384	A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu-Gli protein complexes Tukachinsky, H, Lopez, LV, Salic, A	J. Cell Biol.	2010
24845016	G-protein-coupled receptors, Hedgehog signaling and primary cilia Mukhopadhyay, S, Rohatgi, R	Semin. Cell Dev. Biol.	2014
17641202	Patched1 regulates hedgehog signaling at the primary cilium Rohatgi, R, Milenkovic, L, Scott, MP	Science	2007