Abstract
The G protein-coupled receptor (GPCR) superfamily activates complex signal pathways, yet untangling these signaling systems to understand how specificity in receptor signaling pathways is achieved, has been a challenging question. The roles of membrane trafficking in GPCR signal regulation has undergone a recent paradigm shift, from a mechanism that programs the plasma membrane G protein signaling profile to providing distinct signaling platforms critical for specifying receptor function in vivo. In this chapter, we discuss this evolution of our understanding in the endocytic trafficking systems employed by GPCRs, and how such systems play a deeply integrated role with signaling. We describe recent studies that suggest that the endomembrane compartment can provide a mechanism to both specify, and yet also diversify, GPCR signal transduction. These new evolving models could aid mechanistic understanding of complex disease and provide novel therapeutic avenues.
Keywords
- G Protein-coupled Receptors (GPCR)
- GPCR Signaling
- Signaling Endosomes
- Endosomal Sorting Complex Required For Transport (ESCRT)
- Post-endocytic Sorting
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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- AIP1:
-
Actin-interacting protein 1
- AKT (PKB):
-
Protein kinase B
- ALIX:
-
ALG-interacting protein X
- AMSH:
-
Associated molecule with the SH3 domain of STAM
- AP2:
-
Adaptor protein 2
- APPL1:
-
Adaptor protein containing PH domain, PTB domain, and leucine zipper motif
- ARRDC:
-
Arresting domain containing
- Β1AR, B2AR:
-
Beta adrenergic receptor 1 or 2
- CB1:
-
Cannabinoid receptor 1
- CCP:
-
Clathrin-coated pit
- CXCR4:
-
Chemokine receptor 4
- DOR:
-
δ-opioid receptor
- EE:
-
Early endosome
- EGF:
-
Epidermal growth factor
- EGFR:
-
EGF receptor
- EPB 50:
-
ERM-binding phosphoprotein 50
- ERM:
-
Ezrin–radixin–moesin
- ESCRT:
-
Endosomal sorting complex required for transport
- GAP:
-
GTPase-activating protein
- GASP-1:
-
GPCR-associated sorting protein-1
- GDP:
-
Guanosine diphosphate
- GEF:
-
GDP exchange factor
- GIPC:
-
Gαi-interacting protein C-terminus
- GPCR:
-
G protein-coupled receptors
- GRK:
-
GPCR kinase
- GSK3:
-
Glycogen synthase kinase 3
- GTP:
-
Guanosine triphosphate
- HGF:
-
Hepatocyte growth factor
- Hrs:
-
HGF-regulated tyrosine kinase substrate
- LHR:
-
Luteinizing hormone receptor
- MOR:
-
μ-opioid receptor
- MVB:
-
Multivesicular body
- PAR:
-
Protease-activated receptor
- PDZ:
-
Post-synaptic density 95/disk large/zonula occludens-1
- PI3P:
-
Phosphatidylinositol-3 phosphate
- PKA:
-
Protein kinase A
- PKC:
-
Protein kinase C
- PSD:
-
Post-synaptic density protein 95
- PTHR:
-
Parathyroid hormone receptor
- RGS:
-
Regulator of G protein signaling
- SNX27:
-
Sorting nexin 27
- STAM:
-
Signal-transducing adaptor protein
- STAT:
-
Signal transducer and activator of transcription
- TAB1:
-
TGF-beta-activated kinase 1-binding protein
- TGN:
-
Trans-Golgi network
- TM:
-
Transmembrane
- TSHR:
-
Thyroid-stimulating hormone receptor
- UBD:
-
Ubiquitin-binding domain
- UBPY:
-
Ubiquitin-specific processing protease Y
- V2R:
-
V2 vasopressin receptor
- VASP:
-
Vasodilator-stimulated phosphoprotein
- VEE:
-
Very early endosome
- Vps:
-
Vacuolar protein sorting
- WASH:
-
Wiskott–Aldrich syndrome protein and SCAR homolog
- Wnt:
-
Wingless-related integration site
References
Abdullah N, Beg M, Soares D, Dittman JS, McGraw TE (2016) Downregulation of a GPCR by β-arrestin2-mediated switch from an endosomal to a TGN recycling pathway. Cell Rep 17(11):2966–2978. https://doi.org/10.1016/j.celrep.2016.11.050
Arakaki AKS, Pan WA, Lin H, Trejo J (2018) The α-arrestin ARRDC3 suppresses breast carcinoma invasion by regulating G protein-coupled receptor lysosomal sorting and signaling. J Biol Chem 293(9):3350–3362. https://doi.org/10.1074/jbc.RA117.001516
Barki-Harrington L, Rockman HA (2008) β-Arrestins: multifunctional cellular mediators. Physiology 23:17–22. https://doi.org/10.1152/physiol.00042.2007
Bianco SD, Vandepas L, Correa-Medina M, Gereben B, Mukherjee A, Kuohung W, Carroll R, Teles MG, Latronico AC, Kaiser UB (2011) KISS1R intracellular trafficking and degradation: effect of the Arg386Pro disease-associated mutation. Endocrinology 152(4):1616–1626. https://doi.org/10.1210/en.2010-0903
Birnbaumer L (2007) The discovery of signal transduction by G proteins: a personal account and an overview of the initial findings and contributions that led to our present understanding. Biochim Biophys Acta 1768(4):756–771. https://doi.org/10.1016/j.bbamem.2006.09.027
Boucrot E, Ferreira AP, Almeida-Souza L, Debard S, Vallis Y, Howard G, Bertot L, Sauvonnet N, McMahon HT (2015) Endophilin marks and controls a clathrin-independent endocytic pathway. Nature 517(7535):460–465. https://doi.org/10.1038/nature14067
Bowman SL, Shiwarski DJ, Puthenveedu MA (2016) Distinct G protein-coupled receptor recycling pathways allow spatial control of downstream G protein signaling. J Cell Biol 214(7):797–806. https://doi.org/10.1083/jcb.201512068
Cadigan KM (2010) Receptor endocytosis: frizzled joins the ubiquitin club. EMBO J 29(13):2099–2100. https://doi.org/10.1038/emboj.2010.132
Calebiro D, Nikolaev VO, Gagliani MC, de Filippis T, Dees C, Tacchetti C, Persani L, Lohse MJ (2009) Persistent cAMP-signals triggered by internalized G-protein-coupled receptors. PLoS Biol 7(8):e1000172. https://doi.org/10.1371/journal.pbio.1000172
Cao TT, Deacon HW, Reczek D, Bretscher A, von Zastrow M (1999) A kinase-regulated PDZ-domain interaction controls endocytic sorting of the β2-adrenergic receptor. Nature 401(6750):286–290. https://doi.org/10.1038/45816
Charfi I, Abdallah K, Gendron L, Pineyro G (2018) Delta opioid receptors recycle to the membrane after sorting to the degradation path. Cell Mol Life Sci: CMLS 75(12):2257–2271. https://doi.org/10.1007/s00018-017-2732-5
Cho DI, Zheng M, Min C, Kwon KJ, Shin CY, Choi HK, Kim KM (2013) ARF6 and GASP-1 are post-endocytic sorting proteins selectively involved in the intracellular trafficking of dopamine D(2) receptors mediated by GRK and PKC in transfected cells. Br J Pharmacol 168(6):1355–1374. https://doi.org/10.1111/bph.12025
Coke CJ, Scarlett KA, Chetram MA, Jones KJ, Sandifer BJ, Davis AS, Marcus AI, Hinton CV (2016) Simultaneous activation of induced heterodimerization between CXCR4 chemokine receptor and cannabinoid receptor 2 (CB2) reveals a mechanism for regulation of tumor progression. J Biol Chem 291(19):9991–10005. https://doi.org/10.1074/jbc.M115.712661
Delgado-Peraza F, Ahn KH, Nogueras-Ortiz C, Mungrue IN, Mackie K, Kendall DA, Yudowski GA (2016) Mechanisms of biased β-arrestin-mediated signaling downstream from the cannabinoid 1 receptor. Mol Pharmacol 89(6):618–629. https://doi.org/10.1124/mol.115.103176
DeWire SM, Yamashita DS, Rominger DH, Liu G, Cowan CL, Graczyk TM, Chen XT, Pitis PM, Gotchev D, Yuan C, Koblish M, Lark MW, Violin JD (2013) A G protein-biased ligand at the μ-opioid receptor is potently analgesic with reduced gastrointestinal and respiratory dysfunction compared with morphine. J Pharmacol Exp Ther 344(3):708–717. https://doi.org/10.1124/jpet.112.201616
Dobrowolski R, Vick P, Ploper D, Gumper I, Snitkin H, Sabatini DD, De Robertis EM (2012) Presenilin deficiency or lysosomal inhibition enhances Wnt signaling through relocalization of GSK3 to the late-endosomal compartment. Cell Rep 2(5):1316–1328. https://doi.org/10.1016/j.celrep.2012.09.026
Dores MR, Trejo J (2015) GPCR sorting at multivesicular endosomes. Methods Cell Biol 130:319–332. https://doi.org/10.1016/bs.mcb.2015.05.006
Dores MR, Chen B, Lin H, Soh UJ, Paing MM, Montagne WA, Meerloo T, Trejo J (2012a) ALIX binds a YPX(3)L motif of the GPCR PAR1 and mediates ubiquitin-independent ESCRT-III/MVB sorting. J Cell Biol 197(3):407–419. https://doi.org/10.1083/jcb.201110031
Dores MR, Paing MM, Lin H, Montagne WA, Marchese A, Trejo J (2012b) AP-3 regulates PAR1 ubiquitin-independent MVB/lysosomal sorting via an ALIX-mediated pathway. Mol Biol Cell 23(18):3612–3623. https://doi.org/10.1091/mbc.E12-03-0251
Dores MR, Lin H, Grimsey NJ, Mendez F, Trejo J (2015) The α-arrestin ARRDC3 mediates ALIX ubiquitination and G protein-coupled receptor lysosomal sorting. Mol Biol Cell 26(25):4660–4673. https://doi.org/10.1091/mbc.E15-05-0284
Dunn HA, Ferguson SS (2015) PDZ protein regulation of G protein-coupled receptor trafficking and signaling pathways. Mol Pharmacol 88(4):624–639. https://doi.org/10.1124/mol.115.098509
Eichel K, Jullie D, von Zastrow M (2016) β-Arrestin drives MAP kinase signaling from clathrin-coated structures after GPCR dissociation. Nat Cell Biol 18(3):303–310. https://doi.org/10.1038/ncb3307
Eichel K, Jullie D, Barsi-Rhyne B, Latorraca NR, Masureel M, Sibarita JB, Dror RO, von Zastrow M (2018) Catalytic activation of β-arrestin by GPCRs. Nature. https://doi.org/10.1038/s41586-018-0079-1
Feinstein TN, Wehbi VL, Ardura JA, Wheeler DS, Ferrandon S, Gardella TJ, Vilardaga JP (2011) Retromer terminates the generation of cAMP by internalized PTH receptors. Nat Chem Biol 7(5):278–284. https://doi.org/10.1038/nchembio.545
Feinstein TN, Yui N, Webber MJ, Wehbi VL, Stevenson HP, King JD Jr, Hallows KR, Brown D, Bouley R, Vilardaga JP (2013) Noncanonical control of vasopressin receptor type 2 signaling by retromer and arrestin. J Biol Chem 288(39):27849–27860. https://doi.org/10.1074/jbc.M112.445098
Feng X, Zhang M, Guan R, Segaloff DL (2013) Heterodimerization between the lutropin and follitropin receptors is associated with an attenuation of hormone-dependent signaling. Endocrinology 154(10):3925–3930. https://doi.org/10.1210/en.2013-1407
Ferrandon S, Feinstein TN, Castro M, Wang B, Bouley R, Potts JT, Gardella TJ, Vilardaga JP (2009) Sustained cyclic AMP production by parathyroid hormone receptor endocytosis. Nat Chem Biol 5(10):734–742. https://doi.org/10.1038/nchembio.206
Ferre S, Casado V, Devi LA, Filizola M, Jockers R, Lohse MJ, Milligan G, Pin JP, Guitart X (2014) G protein-coupled receptor oligomerization revisited: functional and pharmacological perspectives. Pharmacol Rev 66(2):413–434. https://doi.org/10.1124/pr.113.008052
Flinn RJ, Backer JM (2010) mTORC1 signals from late endosomes: taking a TOR of the endocytic system. Cell Cycle 9(10):1869–1870. https://doi.org/10.4161/cc.9.10.11679
Flores-Otero J, Ahn KH, Delgado-Peraza F, Mackie K, Kendall DA, Yudowski GA (2014) Ligand-specific endocytic dwell times control functional selectivity of the cannabinoid receptor 1. Nature Commun 5:4589. https://doi.org/10.1038/ncomms5589
Fredriksson R, Lagerstrom MC, Lundin LG, Schioth HB (2003) The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Mol Pharmacol 63(6):1256–1272. https://doi.org/10.1124/mol.63.6.1256
Gage RM, Kim KA, Cao TT, von Zastrow M (2001) A transplantable sorting signal that is sufficient to mediate rapid recycling of G protein-coupled receptors. J Biol Chem 276(48):44712–44720. https://doi.org/10.1074/jbc.M107417200
Galet C, Min L, Narayanan R, Kishi M, Weigel NL, Ascoli M (2003) Identification of a transferable two-amino-acid motif (GT) present in the C-terminal tail of the human lutropin receptor that redirects internalized G protein-coupled receptors from a degradation to a recycling pathway. Mol Endocrinol 17(3):411–422. https://doi.org/10.1210/me.2002-0161
Galet C, Hirakawa T, Ascoli M (2004) The postendocytotic trafficking of the human lutropin receptor is mediated by a transferable motif consisting of the C-terminal cysteine and an upstream leucine. Mol Endocrinol 18(2):434–446. https://doi.org/10.1210/me.2003-0293
Gidon A, Al-Bataineh MM, Jean-Alphonse FG, Stevenson HP, Watanabe T, Louet C, Khatri A, Calero G, Pastor-Soler NM, Gardella TJ, Vilardaga JP (2014) Endosomal GPCR signaling turned off by negative feedback actions of PKA and v-ATPase. Nat Chem Biol 10(9):707–709. https://doi.org/10.1038/nchembio.1589
Girnita L, Shenoy SK, Sehat B, Vasilcanu R, Girnita A, Lefkowitz RJ, Larsson O (2005) β-Arrestin is crucial for ubiquitination and down-regulation of the insulin-like growth factor-1 receptor by acting as adaptor for the MDM2 E3 ligase. J Biol Chem 280(26):24412–24419. https://doi.org/10.1074/jbc.M501129200
Gomes I, Ayoub MA, Fujita W, Jaeger WC, Pfleger KD, Devi LA (2016) G protein-coupled receptor heteromers. Annu Rev Pharmacol Toxicol 56:403–425. https://doi.org/10.1146/annurev-pharmtox-011613-135952
Gorvin CM, Rogers A, Hastoy B, Tarasov AI, Frost M, Sposini S, Inoue A, Whyte MP, Rorsman P, Hanyaloglu AC, Breitwieser GE, Thakker RV (2018) AP2? Mutations impair calcium-sensing receptor trafficking and signaling, and show an endosomal pathway to spatially direct G-protein selectivity. Cell Rep 22(4):1054–1066. https://doi.org/10.1016/j.celrep.2017.12.089
Grundmann M, Merten N, Malfacini D, Inoue A, Preis P, Simon K, Ruttiger N, Ziegler N, Benkel T, Schmitt NK, Ishida S, Muller I, Reher R, Kawakami K, Inoue A, Rick U, Kuhl T, Imhof D, Aoki J, Konig GM, Hoffmann C, Gomeza J, Wess J, Kostenis E (2018) Lack of β-arrestin signaling in the absence of active G proteins. Nature Commun 9(1):341. https://doi.org/10.1038/s41467-017-02661-3
Guo W, Urizar E, Kralikova M, Mobarec JC, Shi L, Filizola M, Javitch JA (2008) Dopamine D2 receptors form higher order oligomers at physiological expression levels. EMBO J 27(17):2293–2304. https://doi.org/10.1038/emboj.2008.153
Hanyaloglu AC (2018) Advances in Membrane Trafficking and Endosomal Signaling of G Protein-Coupled Receptors. Int Rev Cell Mol Biol 339:93–131. https://doi.org/10.1016/bs.ircmb.2018.03.001
Hanyaloglu AC, von Zastrow M (2007) A novel sorting sequence in the β2-adrenergic receptor switches recycling from default to the Hrs-dependent mechanism. J Biol Chem 282(5):3095–3104. https://doi.org/10.1074/jbc.M605398200
Hanyaloglu AC, von Zastrow M (2008) Regulation of GPCRs by endocytic membrane trafficking and its potential implications. Annu Rev Pharmacol Toxicol 48:537–568. https://doi.org/10.1146/annurev.pharmtox.48.113006.094830
Hanyaloglu AC, McCullagh E, von Zastrow M (2005) Essential role of Hrs in a recycling mechanism mediating functional resensitization of cell signaling. EMBO J 24(13):2265–2283. https://doi.org/10.1038/sj.emboj.7600688
Hanyu R, Wehbi VL, Hayata T, Moriya S, Feinstein TN, Ezura Y, Nagao M, Saita Y, Hemmi H, Notomi T, Nakamoto T, Schipani E, Takeda S, Kaneko K, Kurosawa H, Karsenty G, Kronenberg HM, Vilardaga JP, Noda M (2012) Anabolic action of parathyroid hormone regulated by the β2-adrenergic receptor. Proc Natl Acad Sci USA 109(19):7433–7438. https://doi.org/10.1073/pnas.1109036109
Hasdemir B, Bunnett NW, Cottrell GS (2007) Hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) mediates post-endocytic trafficking of protease-activated receptor 2 and calcitonin receptor-like receptor. J Biol Chem 282(40):29646–29657. https://doi.org/10.1074/jbc.M702974200
He J, Bellini M, Inuzuka H, Xu J, Xiong Y, Yang X, Castleberry AM, Hall RA (2006) Proteomic analysis of β1-adrenergic receptor interactions with PDZ scaffold proteins. J Biol Chem 281(5):2820–2827. https://doi.org/10.1074/jbc.M509503200
He C, Wei Y, Sun K, Li B, Dong X, Zou Z, Liu Y, Kinch LN, Khan S, Sinha S, Xavier RJ, Grishin NV, Xiao G, Eskelinen EL, Scherer PE, Whistler JL, Levine B (2013) Beclin 2 functions in autophagy, degradation of G protein-coupled receptors, and metabolism. Cell 154(5):1085–1099. https://doi.org/10.1016/j.cell.2013.07.035
Henne WM, Stenmark H, Emr SD (2013) Molecular mechanisms of the membrane sculpting ESCRT pathway. Cold Spring Harb Perspect Biol 5(9). https://doi.org/10.1101/cshperspect.a016766
Henry AG, White IJ, Marsh M, von Zastrow M, Hislop JN (2011) The role of ubiquitination in lysosomal trafficking of delta-opioid receptors. Traffic 12(2):170–184. https://doi.org/10.1111/j.1600-0854.2010.01145.x
Henry AG, Hislop JN, Grove J, Thorn K, Marsh M, von Zastrow M (2012) Regulation of endocytic clathrin dynamics by cargo ubiquitination. Dev Cell 23(3):519–532. https://doi.org/10.1016/j.devcel.2012.08.003
Hirakawa T, Galet C, Kishi M, Ascoli M (2003a) GIPC binds to the human lutropin receptor (hLHR) through an unusual PDZ domain binding motif, and it regulates the sorting of the internalized human choriogonadotropin and the density of cell surface hLHR. J Biol Chem 278(49):49348–49357. https://doi.org/10.1074/jbc.M306557200
Hirakawa T, Galet C, Kishi M, Ascoli M (2003b) GIPC binds to the human lutropin receptor (hLHR) through an unusual PDZ domain binding motif, and it regulates the sorting of the internalized human choriogonadotropin and the density of cell surface hLHR. J Biol Chem 278(49):49348–49357. https://doi.org/10.1074/jbc.M306557200
Hislop JN, Henry AG, Marchese A, von Zastrow M (2009) Ubiquitination regulates proteolytic processing of G protein-coupled receptors after their sorting to lysosomes. J Biol Chem 284(29):19361–19370. https://doi.org/10.1074/jbc.M109.001644
Hislop JN, Henry AG, von Zastrow M (2011) Ubiquitination in the first cytoplasmic loop of μ-opioid receptors reveals a hierarchical mechanism of lysosomal down-regulation. J Biol Chem 286(46):40193–40204. https://doi.org/10.1074/jbc.M111.288555
Huang SH, Zhao L, Sun ZP, Li XZ, Geng Z, Zhang KD, Chao MV, Chen ZY (2009) Essential role of Hrs in endocytic recycling of full-length TrkB receptor but not its isoform TrkB.T1. J Biol Chem 284(22):15126–15136. https://doi.org/10.1074/jbc.M809763200
Insel PA, Wilderman A, Zambon AC, Snead AN, Murray F, Aroonsakool N, McDonald DS, Zhou S, McCann T, Zhang L, Sriram K, Chinn AM, Michkov AV, Lynch RM, Overland AC, Corriden R (2015) G protein-coupled receptor (GPCR) expression in native cells: “novel” endoGPCRs as physiologic regulators and therapeutic targets. Mol Pharmacol 88(1):181–187. https://doi.org/10.1124/mol.115.098129
Irannejad R, Tomshine JC, Tomshine JR, Chevalier M, Mahoney JP, Steyaert J, Rasmussen SG, Sunahara RK, El-Samad H, Huang B, von Zastrow M (2013) Conformational biosensors reveal GPCR signaling from endosomes. Nature 495(7442):534–538. https://doi.org/10.1038/nature12000
Jean-Alphonse FG, Bowersox S, Chen S, Beard G, Puthenveedu MA, Hanyaloglu AC (2014) Spatially restricted G protein-coupled receptor activity via divergent endocytic compartments. J Biol Chem 289(7):3960–3977. https://doi.org/10.1074/jbc.M113.526350
Jean-Alphonse FG, Wehbi VL, Chen J, Noda M, Taboas JM, Xiao K, Vilardaga J-P (2016) β2-adrenergic receptor control of endosomal PTH receptor signaling via Gβγ. Nat Chem Biol. https://doi.org/10.1038/nchembio.2267
Jensen DD, Lieu T, Halls ML, Veldhuis NA, Imlach WL, Mai QN, Poole DP, Quach T, Aurelio L, Conner J, Herenbrink CK, Barlow N, Simpson JS, Scanlon MJ, Graham B, McCluskey A, Robinson PJ, Escriou V, Nassini R, Materazzi S, Geppetti P, Hicks GA, Christie MJ, Porter CJH, Canals M, Bunnett NW (2017) Neurokinin 1 receptor signaling in endosomes mediates sustained nociception and is a viable therapeutic target for prolonged pain relief. Sci Transl Med 9(392). https://doi.org/10.1126/scitranslmed.aal3447
Ji B, Liu H, Zhang R, Jiang Y, Wang C, Li S, Chen J, Bai B (2017) Novel signalling of dynorphin at κ-opioid receptor/bradykinin B2 receptor heterodimers. Cell Signal 31:66–78. https://doi.org/10.1016/j.cellsig.2017.01.005
Jonas KC, Fanelli F, Huhtaniemi IT, Hanyaloglu AC (2015) Single molecule analysis of functionally asymmetric G protein-coupled receptor (GPCR) oligomers reveals diverse spatial and structural assemblies. J Biol Chem 290(7):3875–3892. https://doi.org/10.1074/jbc.M114.622498
Kennedy JE, Marchese A (2015) Regulation of GPCR trafficking by ubiquitin. Prog Mol Biol Transl Sci 132:15–38. https://doi.org/10.1016/bs.pmbts.2015.02.005
Kuna RS, Girada SB, Asalla S, Vallentyne J, Maddika S, Patterson JT, Smiley DL, DiMarchi RD, Mitra P (2013) Glucagon-like peptide-1 receptor-mediated endosomal cAMP generation promotes glucose-stimulated insulin secretion in pancreatic β-cells. Am J Physiol Endocrinol Metab 305(2):161–170. https://doi.org/10.1152/ajpendo.00551.2012
Lakadamyali M, Rust MJ, Zhuang X (2006) Ligands for clathrin-mediated endocytosis are differentially sorted into distinct populations of early endosomes. Cell 124(5):997–1009. https://doi.org/10.1016/j.cell.2005.12.038
Lally CC, Bauer B, Selent J, Sommer ME (2017) C-edge loops of arrestin function as a membrane anchor. Nature Commun 8:14258. https://doi.org/10.1038/ncomms14258
Lauffer BE, Melero C, Temkin P, Lei C, Hong W, Kortemme T, von Zastrow M (2010) SNX27 mediates PDZ-directed sorting from endosomes to the plasma membrane. J Cell Biol 190(4):565–574. https://doi.org/10.1083/jcb.201004060
Lu A, Tebar F, Alvarez-Moya B, Lopez-Alcala C, Calvo M, Enrich C, Agell N, Nakamura T, Matsuda M, Bachs O (2009) A clathrin-dependent pathway leads to KRas signaling on late endosomes en route to lysosomes. J Cell Biol 184(6):863–879. https://doi.org/10.1083/jcb.200807186
Luttrell LM, Lefkowitz RJ (2002) The role of β-arrestins in the termination and transduction of G-protein-coupled receptor signals. J Cell Sci 115(Pt 3):455–465
Luttrell LM, Ferguson SS, Daaka Y, Miller WE, Maudsley S, Della Rocca GJ, Lin F, Kawakatsu H, Owada K, Luttrell DK, Caron MG, Lefkowitz RJ (1999) β-Arrestin-dependent formation of β2 adrenergic receptor-Src protein kinase complexes. Science 283(5402):655–661
Lyga S, Volpe S, Werthmann RC, Gotz K, Sungkaworn T, Lohse MJ, Calebiro D (2016) Persistent cAMP signaling by internalized LH receptors in ovarian follicles. Endocrinology 157(4):1613–1621. https://doi.org/10.1210/en.2015-1945
Marchese A, Paing MM, Temple BR, Trejo J (2008) G protein-coupled receptor sorting to endosomes and lysosomes. Annu Rev Pharmacol Toxicol 48:601–629. https://doi.org/10.1146/annurev.pharmtox.48.113006.094646
McArdle CA, Franklin J, Green L, Hislop JN (2002) The gonadotrophin-releasing hormone receptor: signalling, cycling and desensitisation. Arch Physiol Biochem 110(1–2):113–122. https://doi.org/10.1076/apab.110.5.5.113.19855
McGarvey JC, Xiao K, Bowman SL, Mamonova T, Zhang Q, Bisello A, Sneddon WB, Ardura JA, Jean-Alphonse F, Vilardaga JP, Puthenveedu MA, Friedman PA (2016) Actin-sorting nexin 27 (SNX27)-retromer complex mediates rapid parathyroid hormone receptor recycling. J Biol Chem 291(21):10986–11002. https://doi.org/10.1074/jbc.M115.697045
Merriam LA, Baran CN, Girard BM, Hardwick JC, May V, Parsons RL (2013) Pituitary adenylate cyclase 1 receptor internalization and endosomal signaling mediate the pituitary adenylate cyclase activating polypeptide-induced increase in guinea pig cardiac neuron excitability. J Neurosci: Official J Soc Neurosci 33(10):4614–4622. https://doi.org/10.1523/JNEUROSCI.4999-12.2013
Min L, Soltis K, Reis AC, Xu S, Kuohung W, Jain M, Carroll RS, Kaiser UB (2014) Dynamic kisspeptin receptor trafficking modulates kisspeptin-mediated calcium signaling. Mol Endocrinol 28(1):16–27. https://doi.org/10.1210/me.2013-1165
Moore CA, Milano SK, Benovic JL (2007) Regulation of receptor trafficking by GRKs and arrestins. Annu Rev Physiol 69:451–482. https://doi.org/10.1146/annurev.physiol.69.022405.154712
Mosser VA, Jones KT, Hoffman KM, McCarty NA, Jackson DA (2008) Differential role of β-arrestin ubiquitination in agonist-promoted down-regulation of M1 vs M2 muscarinic acetylcholine receptors. J Mol Signaling 3:20. https://doi.org/10.1186/1750-2187-3-20
Mukai A, Yamamoto-Hino M, Awano W, Watanabe W, Komada M, Goto S (2010) Balanced ubiquitylation and deubiquitylation of Frizzled regulate cellular responsiveness to Wg/Wnt. EMBO J 29(13):2114–2125. https://doi.org/10.1038/emboj.2010.100
Mundell SJ, Luo J, Benovic JL, Conley PB, Poole AW (2006) Distinct clathrin-coated pits sort different G protein-coupled receptor cargo. Traffic 7(10):1420–1431. https://doi.org/10.1111/j.1600-0854.2006.00469.x
Musheshe N, Schmidt M, Zaccolo M (2018) cAMP: From long-range second messenger to nanodomain signalling. Trends Pharmacol Sci 39(2):209–222. https://doi.org/10.1016/j.tips.2017.11.006
Nakamura K, Liu X, Ascoli M (2000) Seven non-contiguous intracellular residues of the lutropin/choriogonadotropin receptor dictate the rate of agonist-induced internalization and its sensitivity to non-visual arrestins. J Biol Chem 275(1):241–247
Nooh MM, Bahouth SW (2017) Two barcodes encoded by the type-1 PDZ and by phospho-Ser312 regulate retromer/WASH-mediated sorting of the ss1-adrenergic receptor from endosomes to the plasma membrane. Cell Signal 29:192–208. https://doi.org/10.1016/j.cellsig.2016.10.014
Nooh MM, Mancarella S, Bahouth SW (2016) Identification of novel transplantable GPCR recycling motif for drug discovery. Biochem Pharmacol 120:22–32. https://doi.org/10.1016/j.bcp.2016.09.011
Okazaki M, Ferrandon S, Vilardaga JP, Bouxsein ML, Potts JT Jr, Gardella TJ (2008) Prolonged signaling at the parathyroid hormone receptor by peptide ligands targeted to a specific receptor conformation. Proc Natl Acad Sci USA 105(43):16525–16530. https://doi.org/10.1073/pnas.0808750105
Paing MM, Stutts AB, Kohout TA, Lefkowitz RJ, Trejo J (2002) β-Arrestins regulate protease-activated receptor-1 desensitization but not internalization or Down-regulation. J Biol Chem 277(2):1292–1300. https://doi.org/10.1074/jbc.M109160200
Pardon E, Laeremans T, Triest S, Rasmussen SG, Wohlkonig A, Ruf A, Muyldermans S, Hol WG, Kobilka BK, Steyaert J (2014) A general protocol for the generation of nanobodies for structural biology. Nat Protoc 9(3):674–693. https://doi.org/10.1038/nprot.2014.039
Pierce KL, Lefkowitz RJ (2001) Classical and new roles of β-arrestins in the regulation of G-protein-coupled receptors. Nat Rev Neurosci 2(10):727–733. https://doi.org/10.1038/35094577
Puthenveedu MA, von Zastrow M (2006) Cargo regulates clathrin-coated pit dynamics. Cell 127(1):113–124. https://doi.org/10.1016/j.cell.2006.08.035
Puthenveedu MA, Lauffer B, Temkin P, Vistein R, Carlton P, Thorn K, Taunton J, Weiner OD, Parton RG, Von Mark Z (2010) Sequence-dependent sorting of recycling proteins by actin-stabilized endosomal microdomains. Cell 143(5):761–773. https://doi.org/10.1016/j.cell.2010.10.003
Rankovic Z, Brust TF, Bohn LM (2016) Biased agonism: an emerging paradigm in GPCR drug discovery. Bioorg Med Chem Lett 26(2):241–250. https://doi.org/10.1016/j.bmcl.2015.12.024
Reiter E, Ahn S, Shukla A, Lefkowitz R (2012) Molecular mechanism of β-arrestin-biased agonism at seven-transmembrane receptors. Annual Rev Pharmacol Toxicol 52:179–276. https://doi.org/10.1146/annurev.pharmtox.010909.105800
Roman-Vendrell C, Yu YJ, Yudowski GA (2012) Fast modulation of μ-opioid receptor (MOR) recycling is mediated by receptor agonists. J Biol Chem 287(18):14782–14791. https://doi.org/10.1074/jbc.M111.319616
Rosciglione S, Theriault C, Boily MO, Paquette M, Lavoie C (2014) Gαs regulates the post-endocytic sorting of G protein-coupled receptors. Nature Commun 5:4556. https://doi.org/10.1038/ncomms5556
Rusten TE, Vaccari T, Stenmark H (2011) Shaping development with ESCRTs. Nat Cell Biol 14(1):38–45. https://doi.org/10.1038/ncb2381
Shenoy SK (2014) Arrestin interaction with E3 ubiquitin ligases and deubiquitinases: functional and therapeutic implications. Handb Exp Pharmacol 219:187–203. https://doi.org/10.1007/978-3-642-41199-1_10
Shenoy SK, Modi AS, Shukla AK, Xiao K, Berthouze M, Ahn S, Wilkinson KD, Miller WE, Lefkowitz RJ (2009) Β-arrestin-dependent signaling and trafficking of 7-transmembrane receptors is reciprocally regulated by the deubiquitinase USP33 and the E3 ligase Mdm2. Proc Natl Acad Sci USA 106(16):6650–6655. https://doi.org/10.1073/pnas.0901083106
Soergel DG, Subach RA, Cowan CL, Violin JD, Lark MW (2013) First clinical experience with TRV027: pharmacokinetics and pharmacodynamics in healthy volunteers. J Clin Pharmacol 53(9):892–899. https://doi.org/10.1002/jcph.111
Sposini S, Jean-Alphonse FG, Ayoub MA, Oqua A, West C, Lavery S, Brosens JJ, Reiter E, Hanyaloglu AC (2017) Integration of GPCR signaling and sorting from very early endosomes via opposing APPL1 mechanisms. Cell Rep 21(10):2855–2867. https://doi.org/10.1016/j.celrep.2017.11.023
Stallaert W, Christopoulos A, Bouvier M (2011) Ligand functional selectivity and quantitative pharmacology at G protein-coupled receptors. Expert Opin Drug Discov 6(8):811–825. https://doi.org/10.1517/17460441.2011.586691
Stevens RC, Cherezov V, Katritch V, Abagyan R, Kuhn P, Rosen H, Wuthrich K (2013) The GPCR network: a large-scale collaboration to determine human GPCR structure and function. Nat Rev Drug Discov 12(1):25–34. https://doi.org/10.1038/nrd3859
Stoeber M, Jullie D, Lobingier BT, Laeremans T, Steyaert J, Schiller PW, Manglik A, von Zastrow M (2018) A genetically encoded biosensor reveals location bias of opioid drug action. Neuron. https://doi.org/10.1016/j.neuron.2018.04.021
Taelman VF, Dobrowolski R, Plouhinec JL, Fuentealba LC, Vorwald PP, Gumper I, Sabatini DD, De Robertis EM (2010) Wnt signaling requires sequestration of glycogen synthase kinase 3 inside multivesicular endosomes. Cell 143(7):1136–1148. https://doi.org/10.1016/j.cell.2010.11.034
Tappe-Theodor A, Agarwal N, Katona I, Rubino T, Martini L, Swiercz J, Mackie K, Monyer H, Parolaro D, Whistler J, Kuner T, Kuner R (2007) A molecular basis of analgesic tolerance to cannabinoids. J Neurosci: Official J Soc Neurosci 27(15):4165–4177. https://doi.org/10.1523/JNEUROSCI.5648-06.2007
Temkin P, Lauffer B, Jager S, Cimermancic P, Krogan NJ, von Zastrow M (2011) SNX27 mediates retromer tubule entry and endosome-to-plasma membrane trafficking of signalling receptors. Nat Cell Biol 13(6):715–721. https://doi.org/10.1038/ncb2252
Thomsen ARB, Plouffe B, Cahill TJ, Shukla AK, Tarrasch JT, Dosey AM, Kahsai AW, Strachan RT, Pani B, Mahoney JP, Huang L, Breton B, Heydenreich FM, Sunahara RK, Skiniotis G, Bouvier M, Lefkowitz RJ (2016) GPCR-G protein-β-arrestin super-complex mediates sustained G protein signaling. Cell 166(4):907–919. https://doi.org/10.1016/j.cell.2016.07.004
Tian X, Irannejad R, Bowman SL, Du Y, Puthenveedu MA, von Zastrow M, Benovic JL (2016) The α-arrestin ARRDC3 regulates the endosomal residence time and intracellular signaling of the β2-adrenergic receptor. J Biol Chem 291(28):14510–14525. https://doi.org/10.1074/jbc.M116.716589
Trejo J (2005) Internal PDZ ligands: novel endocytic recycling motifs for G protein-coupled receptors. Mol Pharmacol 67(5):1388–1390. https://doi.org/10.1124/mol.105.011288
Tsvetanova NG, von Zastrow M (2014) Spatial encoding of cyclic AMP signaling specificity by GPCR endocytosis. Nat Chem Biol 10(12):1061–1065. https://doi.org/10.1038/nchembio.1665
Tsvetanova NG, Trester-Zedlitz M, Newton BW, Riordan DP, Sundaram AB, Johnson JR, Krogan NJ, von Zastrow M (2017) G protein-coupled receptor endocytosis confers uniformity in responses to chemically distinct ligands. Mol Pharmacol 91(2):145–156. https://doi.org/10.1124/mol.116.106369
Vines CM, Revankar CM, Maestas DC, LaRusch LL, Cimino DF, Kohout TA, Lefkowitz RJ, Prossnitz ER (2003) N-formyl peptide receptors internalize but do not recycle in the absence of arrestins. J Biol Chem 278(43):41581–41584. https://doi.org/10.1074/jbc.C300291200
Vistein R, Puthenveedu MA (2013) Reprogramming of G protein-coupled receptor recycling and signaling by a kinase switch. Proc Natl Acad Sci USA 110(38):15289–15294. https://doi.org/10.1073/pnas.1306340110
Wang J, Hanada K, Staus DP, Makara MA, Dahal GR, Chen Q, Ahles A, Engelhardt S, Rockman HA (2017) Gαi is required for carvedilol-induced β1 adrenergic receptor β-arrestin biased signaling. Nature Commun 8(1):1706. https://doi.org/10.1038/s41467-017-01855-z
West C, Hanyaloglu AC (2015) Minireview: spatial programming of G Protein-coupled receptor activity: decoding signaling in health and disease. Mol Endocrinol 29(8):1095–1106. https://doi.org/10.1210/ME.2015-1065
Xiang Y, Kobilka B (2003) The PDZ-binding motif of the β2-adrenoceptor is essential for physiologic signaling and trafficking in cardiac myocytes. Proc Natl Acad Sci USA 100(19):10776–10781. https://doi.org/10.1073/pnas.1831718100
Xiao K, McClatchy DB, Shukla AK, Zhao Y, Chen M, Shenoy SK, Yates JR 3rd, Lefkowitz RJ (2007) Functional specialization of β-arrestin interactions revealed by proteomic analysis. Proc Natl Acad Sci USA 104(29):12011–12016. https://doi.org/10.1073/pnas.0704849104
Xiao K, Sun J, Kim J, Rajagopal S, Zhai B, Villen J, Haas W, Kovacs JJ, Shukla AK, Hara MR, Hernandez M, Lachmann A, Zhao S, Lin Y, Cheng Y, Mizuno K, Maayan A, Gygi SP, Lefkowitz RJ (2010) Global phosphorylation analysis of β-arrestin-mediated signaling downstream of a seven transmembrane receptor (7TMR). Proc Natl Acad Sci USA 107(34):15299–15304. https://doi.org/10.1073/pnas.1008461107
Yarwood RE, Imlach WL, Lieu T, Veldhuis NA, Jensen DD, Klein Herenbrink C, Aurelio L, Cai Z, Christie MJ, Poole DP, Porter CJH, McLean P, Hicks GA, Geppetti P, Halls ML, Canals M, Bunnett NW (2017) Endosomal signaling of the receptor for calcitonin gene-related peptide mediates pain transmission. Proc Natl Acad Sci USA 114(46):12309–12314. https://doi.org/10.1073/pnas.1706656114
Zhang X, Sun N, Zheng M, Kim KM (2016) Clathrin-mediated endocytosis is responsible for the lysosomal degradation of dopamine D3 receptor. Biochem Biophys Res Commun 476(4):245–251. https://doi.org/10.1016/j.bbrc.2016.05.104
Zoncu R, Perera RM, Balkin DM, Pirruccello M, Toomre D, De Camilli P (2009) A phosphoinositide switch controls the maturation and signaling properties of APPL endosomes. Cell 136(6):1110–1121. https://doi.org/10.1016/j.cell.2009.01.032
Acknowledgements
This work was supported by grants from the Wellcome Trust (WT085099MA), Genesis Research Trust (P15844) to A.C.H, and an Imperial College London President’s Scholarship to S.S.
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Sposini, S., Hanyaloglu, A.C. (2018). Evolving View of Membrane Trafficking and Signaling Systems for G Protein-Coupled Receptors. In: Lamaze, C., Prior, I. (eds) Endocytosis and Signaling. Progress in Molecular and Subcellular Biology, vol 57. Springer, Cham. https://doi.org/10.1007/978-3-319-96704-2_10
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