GPR161 is internalized

Stable Identifier
Reaction [omitted]
Homo sapiens
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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

Scales, SJ, Wen, X, Rangell, L, Jackson, PK, Loktev, A, Mukhopadhyay, S, Ratti, N

Cell 2013
20889716 TULP3 bridges the IFT-A complex and membrane phosphoinositides to promote trafficking of G protein-coupled receptors into primary cilia

Lane, WS, Scales, SJ, Wen, X, Chih, B, Jackson, PK, Nelson, CD, Mukhopadhyay, S

Genes Dev. 2010
20360384 The output of Hedgehog signaling is controlled by the dynamic association between Suppressor of Fused and the Gli proteins

Milenkovic, L, Rohatgi, R, Scott, MP, Humke, EW, Dorn, KV

Genes Dev. 2010
20956384 A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu-Gli protein complexes

Salic, A, Lopez, LV, Tukachinsky, H

J. Cell Biol. 2010
24845016 G-protein-coupled receptors, Hedgehog signaling and primary cilia

Rohatgi, R, Mukhopadhyay, S

Semin. Cell Dev. Biol. 2014
17641202 Patched1 regulates hedgehog signaling at the primary cilium

Milenkovic, L, Rohatgi, R, Scott, MP

Science 2007
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