GPCR signalling from within the cell

British Journal of Pharmacology

Volumn 175, Issue 21, 2018, Pages 4026-4035

  Jong, Yuh Jiin I ^a   Harmon, Steven K ^a   O'Malley, Karen L ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

G PROTEIN COUPLED RECEPTOR; LIGAND;

ANIMAL; CELLS; DRUG EFFECT; HUMAN; METABOLISM; SIGNAL TRANSDUCTION;

ANIMALS; CELLS; HUMANS; LIGANDS; RECEPTORS, G-PROTEIN-COUPLED; SIGNAL TRANSDUCTION;

EID: 85054778218     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/bph.14023     Document Type: Review

References (97)

1. d'Addio M, Pizzigoni A, Bassi MT, Baschirotto C, Valetti C, Incerti B et al. (2000). Defective intracellular transport and processing of OA1 is a major cause of ocular albinism type 1. Hum Mol Genet 9: 3011–3018.
2. Abadir PM, Foster DB, Crow M, Cooke CA, Rucker JJ, Jain A et al. (2011). Identification and characterization of a functional mitochondrial angiotensin system. Proc Natl Acad Sci U S A 108: 14849–14854.
3. Alexander SPH, Catterall WA, Kelly E, Marrion N, Peters JA, Benson HE et al. (2015a). The Concise Guide to PHARMACOLOGY 2015/16: Voltage-gated ion channels. Br J Pharmacol 172: 5904–5941.
4. Alexander SPH, Davenport AP, Kelly E, Marrion N, Peters JA, Benson HE et al. (2015b). The Concise Guide to PHARMACOLOGY 2015/16: G protein-coupled receptors. Br J Pharmacol 172: 5744–5869.
5. Alexander SPH, Fabbro D, Kelly E, Marrion N, Peters JA, Benson HE et al. (2015c). The Concise Guide to PHARMACOLOGY 2015/16: Enzymes. Br J Pharmacol 172: 6024–6109.
6. Alexander SPH, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E et al. (2015d). The Concise Guide to PHARMACOLOGY 2015/16: Transporters. Br J Pharmacol 172: 6110–6202.
7. Alexander SPH, Peters JA, Kelly E, Marrion N, Benson HE, Faccenda E et al. (2015e). The Concise Guide to PHARMACOLOGY 2015/16: Ligand-gated ion channels. Br J Pharmacol 172: 5870–5903.
8. Ango F, Prézeau L, Muller T, Tu JC, Xiao B, Worley PF et al. (2001). Agonist-independent activation of metabotropic glutamate receptors by the intracellular protein Homer. Nature 411: 962–965.
9. Bahouth SW, Nooh MM (2017). Barcoding of GPCR trafficking and signaling through the various trafficking roadmaps by compartmentalized signaling networks. Cell Signal 36: 42–55.
10. Barlow CA, Laishram RS, Anderson RA (2010). Nuclear phosphoinositides: a signaling enigma wrapped in a compartmental conundrum. Trends Cell Biol 20: 25–35.
11. Belous A, Wakata A, Knox CD, Nicoud IB, Pierce J, Anderson CD et al. (2004). Mitochondrial P2Y-like receptors link cytosolic adenosine nucleotides to mitochondrial calcium uptake. J Cell Biochem 92: 1062–1073.
12. Benard G, Massa F, Puente N, Lourenco J, Bellocchio L, Soria-Gomez E et al. (2012). Mitochondrial CB(1) receptors regulate neuronal energy metabolism. Nat Neurosci 15: 558–564.
13. Bhattacharya M, Peri K, Ribeiro-da-Silva A, Almazan G, Shichi H, Hou X et al. (1999). Localization of functional prostaglandin E2 receptors EP3 and EP4 in the nuclear envelope. J Biol Chem 274: 15719–15724.
14. Bhosle VK, Rivera JC, Chemtob S (2017). New insights into mechanisms of nuclear translocation of G-protein coupled receptors. Small GTPases. https://doi.org/10.1080/21541248.2017.1282402.
15. Bhosle VK, Rivera JC, Zhou TE, Omri S, Sanchez M, Hamel D et al. (2016). Nuclear localization of platelet-activating factor receptor controls retinal neovascularization. Cell Discov 2: 16017.
16. + exchanger in nuclear membranes of heart, hepatic, vascular endothelial, and smooth muscle cells. Can J Physiol Pharmacol 84: 431–441.
17. Boivin B, Vaniotis G, Allen BG, Hébert TE (2008). G protein-coupled receptors in and on the cell nucleus: a new signaling paradigm? J Recept Signal Transduct Res 28: 15–28.
18. Branco AF, Allen BG (2015). G-protein-coupled receptor signaling in cardiac nuclear membranes. J Cardiovasc Pharmacol 65: 101–109.
19. Bychkov E, Zurkovsky L, Garret MB, Ahmed MR, Gurevich EV (2012). Distinct cellular and subcellular distributions of G protein-coupled receptor kinase and arrestin isoforms in the striatum. PLoS One 7: e48912.
20. Calebiro D, Godbole A, Lyga S, Lohse MJ (2015). Trafficking and function of GPCRs in the endosomal compartment. Methods Mol Biol 1234: 97–211.
21. Calebiro D, Nikolaev VO, Persani L, Lohse MJ (2010). Signaling by internalized G protein-coupled receptors. Trends Pharmacol Sci 31: 221–228.
22. Campden R, Audet N, Hébert TE (2015). Nuclear G protein signaling: new tricks for old dogs. J Cardiovasc Pharmacol 65: 110–122.
23. Chidiac P, Hebert TE, Valiquette M, Dennis M, Bouvier M (1994). Inverse agonist activity of beta-adrenergic antagonists. Mol Pharmacol 45: 490–499.
24. Cohen O, Granek R (2014). Nucleus-targeted drug delivery: theoretical optimization of nanoparticles decoration for enhanced intracellular active transport. Nano Lett 14: 2515–2521.
25. De Filippo E, Schiedel AC, Manga P (2017). Interaction between G protein-coupled receptor 143 and tyrosinase: implications for understanding ocular albinism type 1. J Invest Dermatol 137: 457–465.
26. Delcourt N, Thouvenot E, Chanrion B, Galéotti N, Jouin P, Bockaert J et al. (2007). ACAP type I receptor transactivation is essential for IGF-1 receptor signalling and antiapoptotic activity in neurons. EMBO J 26: 1542–1551.
27. Di Benedetto A, Sun L, Zambonin CG, Tamma R, Nico B, Calvano CD et al. (2014). Osteoblast regulation via ligand-activated nuclear trafficking of the oxytocin receptor. Proc Natl Acad Sci U S A 111: 16502–16507.
28. Don-Salu-Hewage AS, Chan SY, McAndrews KM, Chetram MA, Dawson MR, Bethea DA et al. (2013). Cysteine (C)-x-C receptor 4 undergoes transportin 1-dependent nuclear localization and remains functional at the nucleus of metastatic prostate cancer cells. PLoS One 8: e57194.
29. 4 is the major trigger of stress-induced oxidative DNA damage. Nat Commun 6: 10112.
30. Estrada R, Wang L, Jala VR, Lee JF, Lin CY, Gray RD et al. (2009). Ligand-induced nuclear translocation of S1P(1) receptors mediates Cyr61 and CTGF transcription in endothelial cells. Histochem Cell Biol 131: 239–249.
31. Favre N, Camps M, Arod C, Chabert C, Rommel C et al. (2008). Chemokine receptor CCR2 undergoes transportin1-dependent nuclear translocation. Proteomics 8: 4560–4576.
32. Gbahou F, Cecon E, Viault G, Gerbier R, Jean-Alphonse F, Karamitri A et al. (2017). Design and validation of the first cell-impermeant melatonin receptor agonist. Br J Pharmacol 174: 2409–2421.
33. Geppetti P, Veldhuis NA, Lieu T, Bunnett NW (2015). G protein-coupled receptors: dynamic machines for signaling pain and itch. Neuron 88: 635–649.
34. Gobeil F, Fortier A, Zhu T, Bossolasco M, Leduc M, Grandbois M et al. (2006). G-protein-coupled receptors signalling at the cell nucleus: an emerging paradigm. Can J Physiol Pharmacol 84: 287–297.
35. Goshima Y, Nakamura F, Masukawa D, Chen S, Koga M (2014). Cardiovascular actions of DOPA mediated by the gene product of ocular albinism 1. J Pharmacol Sci 126: 14–20.
36. Hebert-Chatelain E, Desprez T, Serrat R, Bellocchio L, Soria-Gomez E, Busquets-Garcia A et al. (2016). A cannabinoid link between mitochondria and memory. Nature 539: 555–559.
37. Hebert-Chatelain E, Reguero L, Puente N, Lutz B, Chaouloff F, Rossignol R et al. (2014a). Cannabinoid control of brain bioenergetics: exploring the subcellular localization of the CB1. Mol Metab 3: 495–504.
38. Hebert-Chatelain E, Reguero L, Puente N, Lutz B, Chaouloff F, Rossignol R et al. (2014b). Studying mitochondrial CB1 receptors: yes we can. Mol Metab 3: 339.
39. Hinshaw JE, Carragher BO, Milligan RA (1992). Architecture and design of the nuclear pore complex. Cell 69: 1133–1141.
40. Hubert GW, Paquet M, Smith Y (2001). Differential subcellular localization of mGluR1a and mGluR5 in the rat and monkey substantia nigra. J Neurosci 21: 1838–1847.
41. Irannejad R, Pessino V, Mika D, Huang B, Wedegaertner PB, Conti M et al. (2017). Functional selectivity of GPCR-directed drug action through location bias. Nat Chem Biol 13: 799–806.
42. Irannejad R, Tomshine JC, Tomshine JR, Chevalier M, Mahoney JP, Steyaert J et al. (2013). Conformational biosensors reveal GPCR signalling from endosomes. Nature 495: 534–538.
43. Jensen DD, Lieu T, Halls ML, Veldhuis NA, Imlach WL, Mai QN et al. (2017). Neurokinin 1 receptor signaling in endosomes mediates sustained nociception and is a viable therapeutic target for prolonged pain relief. Sci Transl Med 9 pii: eaal3447.
44. Jong YI, O'Malley KL (2017). Mechanisms associated with activation of intracellular metabotropic glutamate receptor, mGluR5. Neurochem Res 42: 166–172.
45. Jong YJ, Kumar V, Kingston AE, Romano C, O'Malley KL (2005). Functional metabotropic glutamate receptors on nuclei from brain and primary cultured striatal neurons. Role of transporters in delivering ligand. J Biol Chem 280: 30469–30480.
46. Jong YJ, Schwetye KE, O'Malley KL (2007). Nuclear localization of functional metabotropic glutamate receptor mGlu1 in HEK293 cells and cortical neurons: role in nuclear calcium mobilization and development. J Neurochem 101: 458–469.
47. Jong YJ, Sergin I, Purgert CA, O'Malley KL (2014). Location-dependent signaling of the group 1 metabotropic glutamate receptor mGlu5. Mol Pharmacol 86: 774–785.
48. Joyal JS, Bhosle VK, Chemtob S (2015). Subcellular G-protein coupled receptor signaling hints at greater therapeutic selectivity. Expert Opin Ther Targets 19: 717–721.
49. Joyal JS, Nim S, Zhu T, Sitaras N, Rivera JC, Shao Z et al. (2014). Subcellular localization of coagulation factor II receptor-like 1 in neurons governs angiogenesis. Nat Med 20: 1165–1173.
50. Katta SS, Smoyer CJ, Jaspersen SL (2014). Destination: inner nuclear membrane. Trends Cell Biol 24: 221–229.
51. Kinsey CG, Bussolati G, Bosco M, Kimura T, Pizzorno MC, Chernin MI et al. (2007). Constitutive and ligand-induced nuclear localization of oxytocin receptor. J Cell Mol Med 11: 96–110.
52. 2+ release. J Biol Chem 283: 14072–14083.
53. Lee DK, Lança AJ, Cheng R, Nguyen T, Ji XD, Gobeil F Jr et al. (2004). Agonist-independent nuclear localization of the apelin, angiotensin AT1, and bradykinin B2 receptors. J Biol Chem 279: 7901–7908.
54. López-Bendito G, Shigemoto R, Fairén A, Luján R (2002). Differential distribution of group I metabotropic glutamate receptors during rat cortical development. Cereb Cortex 12: 625–638.
55. Lusk CP, Blobel G, King MC (2007). Highway to the inner nuclear membrane: rules for the road. Nat Rev Mol Cell Biol 8: 414–420.
56. Ma L, Jia J, Niu W, Jiang T, Zhai Q, Yang L et al. (2015). Mitochondrial CB1 receptor is involved in ACEA-induced protective effects on neurons and mitochondrial functions. Sci Rep 5: 12440.
57. Mao LM, Liu XY, Zhang GC, Chu X, Fibuch EE, Wang LS et al. (2008). Phosphorylation of group I metabotropic glutamate receptors (mGluR1/5) in vitro and in vivo. Neuropharmacology 55: 403–408.
58. Melser S, Zottola ACP, Serrat R, Puente N, Grandes P, Marsicano G et al. (2017). Functional analysis of mitochondrial CB1 cannabinoid receptors (mtCB1) in the brain. Methods Enzymol 593: 143–174.
59. 2+ in adult cardiac myocytes. J Mol Cell Cardiol 62: 189–202.
60. Morinelli TA, Raymond JR, Baldys A, Yang Q, Lee MH, Luttrell L et al. (2007). Identification of a putative nuclear localization sequence within ANG II AT(1A) receptor associated with nuclear activation. Am J Physiol Cell Physiol 292: C1398–C1408.
61. 2+ concentration in isolated rat liver nuclei. Proc Natl Acad Sci U S A 86: 453–457.
62. 2+ changes in heterologous cell types and neurons. J Biol Chem 278: 28210–28219.
63. Pedruzzi E, Guichard C, Ollivier V, Driss F, Fay M, Prunet C et al. (2004). NAD(P)H oxidase Nox-4 mediates 7-ketocholesterol-induced endoplasmic reticulum stress and apoptosis in human aortic smooth muscle cells. Mol Cell Biol 24: 10703–10717.
64. Petersen OH, Gerasimenko OV, Gerasimenko JV, Mogami H, Tepikin AV (1998). The calcium store in the nuclear envelope. Cell Calcium 23: 87–90.
65. Poole DP, Bunnett NW (2016). G protein-coupled receptor trafficking and signalling in the enteric nervous system: the past, present and future. Adv Exp Med Biol 891: 145–152.
66. Power JM, Sah P (2002). Nuclear calcium signaling evoked by cholinergic stimulation in hippocampal CA1 pyramidal neurons. J Neurosci 22: 3454–3462.
67. Purgert CA, Izumi Y, Jong YJ, Kumar V, Zorumski CF, O'Malley KL (2014). Intracellular mGlu5 can mediate synaptic plasticity in the hippocampus. J Neurosci 34: 4589–4598.
68. Rankovic Z, Brust TF, Bohn LM (2016). Biased agonism: an emerging paradigm in GPCR drug discovery. Bioorg Med Chem Lett 26: 241–250.
69. Re M, Pampillo M, Savard M, Dubuc C, McArdle CA, Millar RP et al. (2010). The human gonadotropin releasing hormone type I receptor is a functional intracellular GPCR expressed on the nuclear membrane. PLoS One 5: e11489.
70. Reiter E, Ahn S, Shukla AK, Lefkowitz RJ (2012). Molecular mechanism of beta-arrestin-biased agonism at seven-transmembrane receptors. Annu Rev Pharmacol Toxicol 52: 179–197.
71. Samaraweera P, Shen B, Newton JM, Barsh GS, Orlow SJ (2001). The mouse ocular albinism 1 gene product is an endolysosomal protein. Exp Eye Res 72: 319–329.
72. Schiaffino MV, Baschirotto C, Pellegrini G, Montalti S, Tacchetti C, De Luca M et al. (1996). The ocular albinism type 1 gene product is a membrane glycoprotein localized to melanosomes. Proc Natl Acad Sci U S A 93: 9055–9060.
73. Sergin I, Jong YI, Harmon SK, Kumar V, O'Malley KL (2017). Sequences within the C terminus of the metabotropic glutamate receptor 5 (mGluR5) are responsible for inner nuclear membrane localization. J Biol Chem 292: 3637–3655.
74. Shenoy SK, Lefkowitz RJ (2011). β-Arrestin-mediated receptor trafficking and signal transduction. Trends Pharmacol Sci 32: 521–533.
75. Southan C, Sharman JL, Benson HE, Faccenda E, Pawson AJ, Alexander SPH et al. (2016). The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. Nucl Acids Res 44: D1054–D1068.
76. Stewart MP, Sharei A, Ding X, Sahay G, Langer R, Jensen KF (2016). In vitro and ex vivo strategies for intracellular delivery. Nature 538: 183–192.
77. Sun RL, Huang CX, Bao JL, Jiang JY, Zhang B, Zhou SX et al. (2016). CC-chemokine ligand 2 (CCL2) suppresses high density lipoprotein (HDL) internalization and cholesterol efflux via CC-chemokine receptor 2 (CCR2) induction and p42/44 mitogen-activated protein kinase (MAPK) activation in human endothelial cells. J Biol Chem 291: 19532–19544.
78. Tadevosyan A, Létourneau M, Folch B, Doucet N, Villeneuve LR, Mamarbachi AM et al. (2015). Photoreleasable ligands to study intracrine angiotensin II signalling. J Physiol 593: 521–539.
79. Tadevosyan A, Vaniotis G, Allen BG, Hébert TE, Nattel S (2012). G protein-coupled receptor signalling in the cardiac nuclear membrane: evidence and possible roles in physiological and pathophysiological function. J Physiol 590: 1313–1330.
80. Tadevosyan A, Villeneuve LR, Fournier A, Chatenet D, Nattel S, Allen BG (2016). Caged ligands to study the role of intracellular GPCRs. Methods 92: 72–77.
81. Trivedi RR, Bhattacharyya S (2012). Constitutive internalization and recycling of metabotropic glutamate receptor 5 (mGluR5). Biochem Biophys Res Commun 427: 185–190.
82. Tsvetanova NG, von Zastrow M (2014). Spatial encoding of cyclic AMP signaling specificity by GPCR endocytosis. Nat Chem Biol 10: 1061–1065.
83. Vaniotis G, Allen BG, Hébert TE (2011). Nuclear GPCRs in cardiomyocytes: an insider's view of β-adrenergic receptor signaling. Am J Physiol Heart Circ Physiol 301: H1754–H1764.
84. Verzijl D, Peters SL, Alewijnse AE (2010). Sphingosine-1-phosphate receptors: zooming in on ligand-induced intracellular trafficking and its functional implications. Mol Cells 29: 99–104.
85. Vilardaga JP, Jean-Alphonse FG, Gardella TJ (2014). Endosomal generation of cAMP in GPCR signaling. Nat Chem Biol 10: 700–706.
86. Vincent K, Cornea VM, Jong YJ, Laferrière A, Kumar N, Mickeviciute A et al. (2016). Intracellular mGluR5 plays a critical role in neuropathic pain. Nat Commun 7: 10604.
87. Wang F, Wang Y, Zhang X, Zhang W, Guo S, Jin F (2014). Recent progress of cell-penetrating peptides as new carriers for intracellular cargo delivery. J Control Release 174: 126–136.
88. Wang Q, Zhang H, Xu H, Guo D, Shi H, Li Y et al. (2016). 5-HTR3 and 5-HTR4 located on the mitochondrial membrane and functionally regulated mitochondrial functions. Sci Rep 6: 37336.
89. Weyemi U, Lagente-Chevallier O, Boufraqech M, Prenois F, Courtin F et al. (2012). ROS-generating NADPH oxidase NOX4 is a critical mediator in oncogenic H-Ras-induced DNA damage and subsequent senescence. Oncogene 31: 1117–1129.
90. Wright CD, Wu SC, Dahl EF, Sazama AJ, O'Connell TD (2012). Nuclear localization drives α1-adrenergic receptor oligomerization and signaling in cardiac myocytes. Cell Signal 24: 794–802.
91. Wu SC, Dahl EF, Wright CD, Cypher AL, Healy CL, O'Connell TD (2014). Nuclear localization of a1A-adrenergic receptors is required for signaling in cardiac myocytes: an “inside-out” a1-AR signaling pathway. J Am Heart Assoc 3: e000145.
92. Wu SC, OʼConnell TD (2015). Nuclear compartmentalization of α1-adrenergic receptor signaling in adult cardiac myocytes. J Cardiovasc Pharmacol 65: 91–100.
93. Xu Z, Lv XA, Dai Q, Ge YQ, Xu J (2016). Acute upregulation of neuronal mitochondrial type-1 cannabinoid receptor and its role in metabolic defects and neuronal apoptosis after TBI. Mol Brain 9: 75.
94. Ye J, Liu E, Yu Z, Pei X, Chen S, Zhang P et al. (2016). CPP-assisted intracellular drug delivery, what is next? Int J Mol Sci 17: E1892.
95. Yu R, Liu H, Peng X, Cui Y, Song S, Wang L et al. (2017). The palmitoylation of the N-terminal extracellular Cys37 mediates the nuclear translocation of VPAC1 contributing to its anti-apoptotic activity. Oncotarget https://doi.org/10.18632/oncotarget.17449.
96. Zhu T, Gobeil F, Vazquez-Tello A, Leduc M, Rihakova L, Bossolasco M et al. (2006). Intracrine signaling through lipid mediators and their cognate nuclear G-protein-coupled receptors: a paradigm based on PGE2, PAF, and LPA1 receptors. Can J Physiol Pharmacol 84: 377–391.
97. Zuleger N, Kerr AR, Schirmer EC (2012). Many mechanisms, one entrance: membrane protein translocation into the nucleus. Cell Mol Life Sci 69: 2205–2216.