Skip to main content
SpringerLink
Log in

Endocytosis of G Protein-Coupled Receptors and Their Ligands: Is There a Role in Metal Trafficking?

  • Review Paper
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

The prevalence of metal dysregulation in many neurodegenerative and neurocognitive disorders has compelled many studying such diseases to investigate the mechanisms underlying metal regulation in the central nervous system. Metal homoeostasis is often complex, with sophisticated, multilayered pathways in operation. G protein-coupled receptors are omnipresent on cell membranes and have intriguing mechanisms of endocytosis and trafficking that may be useful in metal homoeostasis. Indeed, many receptors and/or their cognate ligands are able to bind metals, and in many cases metals are considered to have neuromodulatory roles as a result of receptor binding. In this mini-review, we outline the structural and functional aspects of G protein-coupled receptors with a focus on the mechanisms leading to endocytosis and cellular trafficking. We further highlight how this may help in the trafficking of metal ions, notably copper.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Birnbaumer, L., Abramowitz, J., & Brown, A. M. (1990). Receptor-effector coupling by G proteins. Biochimica et Biophysica Acta, 1031, 163–224.

    Article  PubMed  CAS  Google Scholar 

  2. Costanzi, S., Siegel, J., Tikhonova, I. G., et al. (2009). Rhodopsin and the others: A historical perspective on structural studies of G protein-coupled receptors. Current Pharmaceutical Design, 15, 3994–4002.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Rosenbaum, D. M., Rasmussen, S. G., & Kobilka, B. K. (2009). The structure and function of G-protein-coupled receptors. Nature, 459, 356–363.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Rasmussen, S. G., DeVree, B. T., Zou, Y., et al. (2011). Crystal structure of the β2adrenergic receptor-Gs protein complex. Nature, 477, 549–555.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Kobilka, B. K. (2007). G protein coupled receptor structure and activation. BBA-Biomembranes, 1768, 794–807.

    Article  PubMed  CAS  Google Scholar 

  6. Gether, U., & Kobilka, B. K. (1998). G protein-coupled receptors II. Mechanism of agonist activation. Journal of Biological Chemistry, 273, 17979–17982.

    Article  PubMed  CAS  Google Scholar 

  7. Kristiansen, K. (2004). Molecular mechanisms of ligand binding, signaling, and regulation within the superfamily of G-protein-coupled receptors: molecular modeling and mutagenesis approaches to receptor structure and function. Pharmacology & Therapeutics, 103, 21–80.

    Article  CAS  Google Scholar 

  8. Venkatakrishnan, A., Deupi, X., Lebon, G., et al. (2013). Molecular signatures of G-protein-coupled receptors. Nature, 494, 185–194.

    Article  PubMed  CAS  Google Scholar 

  9. Kolakowski, J. L. (1994). GCRDb: A G-protein-coupled receptor database. Receptors Channels, 2, 1–7.

    PubMed  CAS  Google Scholar 

  10. Fredriksson, R., Lagerström, M. C., Lundin, L.-G., et al. (2003). The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Molecular Pharmacology, 63, 1256–1272.

    Article  PubMed  CAS  Google Scholar 

  11. Wolf, S., & Grünewald, S. (2015). Sequence, structure and ligand binding evolution of rhodopsin-like G protein-coupled receptors: A crystal structure-based phylogenetic analysis. PLoS ONE, 10, e0123533.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Lappano, R., & Maggiolini, M. (2011). G protein-coupled receptors: Novel targets for drug discovery in cancer. Nature Reviews Drug discovery, 10, 47–60.

    Article  PubMed  CAS  Google Scholar 

  13. Dwivedi, H., Baidya, M., & Shukla, A. K. (2018). GPCR signaling: The interplay of Gai and b-arrestin. Current Biology, 28, R324–R327.

    Article  PubMed  CAS  Google Scholar 

  14. Zhang, Y., Sun, B., Feng, D., et al. (2017). Cryo-EM structure of the activated GLP-1 receptor in complex with a G protein. Nature, 546, 248–253.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Cao, C., Zhang, H., Yang, Z., et al. (2018). Peptide recognition, signaling and modulation of class B G protein-coupled receptors. Current Opinion in Structural Biology, 51, 53–60.

    Article  PubMed  CAS  Google Scholar 

  16. Hazell, G. G., Hindmarch, C. C., Pope, G. R., et al. (2012). G protein-coupled receptors in the hypothalamic paraventricular and supraoptic nuclei—Serpentine gateways to neuroendocrine homeostasis. Frontiers in Neuroendocrinology, 33, 45–66.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Gahbauer, S., & Böckmann, R. A. (2016). Membrane-mediated oligomerization of G protein coupled receptors and its implications for GPCR function. Frontiers in Physiology, 7, 494.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Springael, J.-Y., Urizar, E., & Parmentier, M. (2005). Dimerization of chemokine receptors and its functional consequences. Cytokine and Growth Factor Reviews, 16, 611–623.

    Article  PubMed  CAS  Google Scholar 

  19. Ferre, S. (2015). The GPCR heterotetramer: Challenging classical pharmacology. Trends in Pharmacological Sciences, 36, 145–152.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Perez-Aguilar, J. M., Shan, J., LeVine, M. V., et al. (2014). A functional selectivity mechanism at the serotonin-2A GPCR involves ligand-dependent conformations of intracellular loop 2. Journal of the American Chemical Society, 136, 16044–16054.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Gurevich, V. V., & Gurevich, E. V. (2008). How and why do GPCRs dimerize? Trends in Pharmacological Sciences, 29, 234–240.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Grammatopoulos, D. K. (2017). Regulation of G-protein coupled receptor signalling underpinning neurobiology of mood disorders and depression. Molecular and Cellular Endocrinology, 449, 82–89.

    Article  PubMed  CAS  Google Scholar 

  23. Ng, J., Rashid, A. J., So, C. H., et al. (2010). Activation of calcium/calmodulin-dependent protein kinase IIα in the striatum by the heteromeric D1-D2 dopamine receptor complex. Neuroscience, 165, 535–541.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Damian, M., V. Pons, P. Renault, et al. (2018) GHSR-D2R heteromerization modulates dopamine signaling through an effect on G protein conformation. Proceedings of the National Academy of the United States of America, 115, 4501-4506.

  25. George, S. R., O’Dowd, B. F., & Lee, S. P. (2002). G-protein-coupled receptor oligomerization and its potential for drug discovery. Nature Reviews Drug discovery, 1, 808.

    Article  PubMed  CAS  Google Scholar 

  26. Orekhov, P., Bothe, A., Steinhoff, H. J., et al. (2017). Sensory rhodopsin I and sensory rhodopsin II form trimers of dimers in complex with their cognate transducers. Photochemistry and Photobiology, 93, 796–804.

    Article  PubMed  CAS  Google Scholar 

  27. Pizard, A., Marchetti, J., Allegrini, J., et al. (1998). Negative cooperativity in the human bradykinin b2receptor. The Journal of Biological Chemistry, 273, 1309–1315.

    Article  PubMed  CAS  Google Scholar 

  28. Robbins, M. J., Calver, A. R., Filippov, A. K., et al. (2001). GABAB2 is essential for G-protein coupling of the GABAB receptor heterodimer. The Journal of Neuroscience, 21, 8043–8052.

    Article  PubMed  CAS  Google Scholar 

  29. Tobin, A. (2008). G‐protein‐coupled receptor phosphorylation: Where, when and by whom. British Journal of Pharmacology, 153, S167–S176.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Navarro, G., Cordomi, A., Casado-Anguera, V., et al. (2018). Evidence for functional pre-coupled complexes of receptor heteromers and adenylyl cyclase. Nature Communications, 9, 1242.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Khan, S. M., Sleno, R., Gora, S., et al. (2013). The expanding roles of Gβγ subunits in G protein–coupled receptor signaling and drug action. Pharmacological Reviews, 65, 545–577.

    Article  PubMed  CAS  Google Scholar 

  32. Cabrera-Vera, T. M., Vanhauwe, J., Thomas, T. O., et al. (2003). Insights into G protein structure, function, and regulation. Endocrine Reviews, 24, 765–781.

    Article  PubMed  CAS  Google Scholar 

  33. Mani, I., Garg, R., Tripathi, S., et al. (2015). Subcellular trafficking of guanylyl cyclase/natriuretic peptide receptor-A with concurrent generation of intracellular cGMP. Bioscience Reports, 35, e00260.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Landry, Y., & Gies, J. (2002). Heterotrimeric G proteins control diverse pathways of transmembrane signaling, a base for drug discovery. Mini Reviews in Medicinal Chemistry, 2, 361–372.

    Article  PubMed  CAS  Google Scholar 

  35. Shen, A., Nieves-Cintron, M., Deng, Y., et al. (2018). Functionally distinct and selectively phosphorylated GPCR subpopulations co-exist in a single cell. Nature Communications, 9, 1050.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Cahill, T. J., Thomsen, A. R., Tarrasch, J. T., et al. (2017) Distinct conformations of GPCR–β-arrestin complexes mediate desensitization, signaling, and endocytosis. Proceedings of the National Academy of the United States of America, 114, 2562–2567.

  37. Rajagopal, S., Rajagopal, K., & Lefkowitz, R. J. (2010). Teaching old receptors new tricks: Biasing seven-transmembrane receptors. Nature Reviews Drug discovery, 9, 373–386.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Shenoy, S. K., & Lefkowitz, R. J. (2011). β-Arrestin-mediated receptor trafficking and signal transduction. Trends in Pharmacological Sciences, 32, 521–533.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Tian, X., Kang D. S., & Benovic J. L. (2014). β-Arrestins and G Protein-Coupled Receptor Trafficking. In: Gurevich V. (eds) Arrestins - Pharmacology and Therapeutic Potential. Handbook of Experimental Pharmacology, vol 219. Springer, Berlin, Heidelberg..

  40. Ferreira, F., Foley, M., Cooke, A., et al. (2012). Endocytosis of G protein-coupled receptors is regulated by clathrin light chain phosphorylation. Current Biology, 22, 1361–1370.

    Article  PubMed  CAS  Google Scholar 

  41. Claing, A., Perry, S. J., Achiriloaie, M., et al. (2000). Multiple endocytic pathways of G protein-coupled receptors delineated by GIT1 sensitivity. Proceedings of the National Academy of the United States of America, 97, 1119–1124.

    Article  CAS  Google Scholar 

  42. Takei, K., Slepnev, V. I., Haucke, V., et al. (1999). Functional partnership between amphiphysin and dynamin in clathrin-mediated endocytosis. Nature Cell Biology, 1, 33–39.

    Article  PubMed  CAS  Google Scholar 

  43. Reider, A., & Wendland, B. (2011). Endocytic adaptors--Social networking at the plasma membrane. Journal of Cell Science, 124, 1613–1622.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. McMahon, H. T., & Boucrot, E. (2011). Molecular mechanism and physiological functions of clathrin-mediated endocytosis. Nature Reviews Molecular Cell Biology, 12, 517–533.

    Article  PubMed  CAS  Google Scholar 

  45. Schmid, S. L. (2017) Reciprocal regulation of signaling and endocytosis: Implications for the evolving cancer cell. Journal of Cell Biology, https://doi.org/10.1083/jcb.201705017.

  46. Latek, D., Modzelewska, A., Trzaskowski, B., et al. (2012). G protein-coupled receptors—Recent advances. Acta Biochimica Polonica, 59, 515.

    PubMed  PubMed Central  CAS  Google Scholar 

  47. Faklaris, O., Cottet, M., Falco, A., et al. (2015). Multicolor time-resolved Förster resonance energy transfer microscopy reveals the impact of GPCR oligomerization on internalization processes. The FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 29, 2235–2246.

    Article  CAS  Google Scholar 

  48. Hofman, E. G., Bader, A. N., Voortman, J., et al. (2010). Ligand-induced EGF receptor oligomerization is kinase-dependent and enhances internalization. The Journal of Biological Chemistry, 285, 39481–39489.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Xu, S., Olenyuk, B. Z., Okamoto, C. T., et al. (2013). Targeting receptor-mediated endocytotic pathways with nanoparticles: Rationale and advances. Advanced Drug Delivery Reviews, 65, 121–138.

    Article  PubMed  CAS  Google Scholar 

  50. Cook, J. L. (2010). G Protein–coupled receptors as disease targets: Emerging paradigms. The Ochsner Journal, 10, 2–7.

    PubMed  PubMed Central  Google Scholar 

  51. Wandinger-Ness, A., & Zerial, M. (2014). Rab proteins and the compartmentalization of the endosomal system. Cold Spring Harbor Perspectives in Biology, 6, a022616.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Calebiro, D., Nikolaev, V. O., Persani, L., et al. (2010). Signaling by internalized G-protein-coupled receptors. Trends in Pharmacological Sciences, 31, 221–228.

    Article  PubMed  CAS  Google Scholar 

  53. Nazarewicz, R. R., Salazar, G., Patrushev, N., et al. (2011). Early endosomal antigen 1 (EEA1) is an obligate scaffold for angiotensin II-induced, PKC-α-dependent Akt activation in endosomes. The Journal of Biological Chemistry, 286, 2886–2895.

    Article  PubMed  CAS  Google Scholar 

  54. Wang, Y., Yamaguchi, H., Hsu, J., et al. (2010). Nuclear trafficking of the epidermal growth factor receptor family membrane proteins. Oncogene, 29, 3997–4006.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Hymel, D., & Peterson, B. R. (2012). Synthetic cell surface receptors for delivery of therapeutics and probes. Advanced Drug Delivery Reviews, 64, 797–810.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Jongsma, M. L., Berlin, I., Wijdeven, R. H., et al. (2016). An ER-associated pathway defines endosomal architecture for controlled cargo transport. Cell, 166, 152–166.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Cheng, S.-B., Graeber, C. T., Quinn, J. A., et al. (2011). Retrograde transport of the transmembrane estrogen receptor, G-protein-coupled-receptor-30 (GPR30/GPER) from the plasma membrane towards the nucleus. Steroids, 76, 892–896.

    PubMed  CAS  Google Scholar 

  58. Bhosle, V. K., Rivera, J. C., and Chemtob, S. (2017) New insights into mechanisms of nuclear translocation of G-protein coupled receptors. Small GTPases, 1-10.

  59. Bhosle, V. K., Rivera, J. C., Zhou, T. E., et al. (2016). Nuclear localization of platelet-activating factor receptor controls retinal neovascularization. Cell Discovery, 2, 16017.

    Article  PubMed  Google Scholar 

  60. Brand, T. M., Iida, M., Li, C., et al. (2011). The nuclear epidermal growth factor receptor signaling network and its role in cancer. Discovery Medicine, 12, 419–432.

    PubMed  PubMed Central  Google Scholar 

  61. Flynn, F. W., Jensen, D. D., Thakar, A., et al. (2011). Neurokinin 3 receptor forms a complex with acetylated histone H3 and H4 in hypothalamic neurons following hyperosmotic challenge. American Journal of Physiology Regulatory, Integrative and Comparative Physiology, 301, R822–R831.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Boivin, B., Vaniotis, G., Allen, B. G., et al. (2008). G protein-coupled receptors in and on the cell nucleus: A new signaling paradigm? Journal of Recept Signal Transduction, 28, 15–28.

    Article  CAS  Google Scholar 

  63. Qian, Z. M., Li, H., Sun, H., et al. (2002). Targeted drug delivery via the transferrin receptor-mediated endocytosis pathway. Pharmacological Reviews, 54, 561–587.

    Article  PubMed  CAS  Google Scholar 

  64. Lamb, J., Ray, F., Ward, J. H., et al. (1983). Internalization and subcellular localization of transferrin and transferrin receptors in HeLa cells. The Journal of Biological Chemistry, 258, 8751–8758.

    PubMed  CAS  Google Scholar 

  65. Wang, J., & Pantopoulos, K. (2011). Regulation of cellular iron metabolism. The Biochemical Journal, 434, 365–381.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Tortorella, S., & Karagiannis, T. C. (2014). Transferrin receptor-mediated endocytosis: a useful target for cancer therapy. The Journal of Membrane Biology, 247, 291–307.

    Article  PubMed  CAS  Google Scholar 

  67. Harding, C., Heuser, J., & Stahl, P. (1983). Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. The Journal of Cell Biology, 97, 329–339.

    Article  PubMed  CAS  Google Scholar 

  68. Nagabhushana, A., Chalasani, M. L., Jain, N., et al. (2010). Regulation of endocytic trafficking of transferrin receptor by optineurin and its impairment by a glaucoma-associated mutant. BMC Cell Biology, 11, 4.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Matson Dzebo, M., Arioz, C., Wittung-Stafshede, P. (2016). Extended functional repertoire for human copper chaperones. Biomolecular Concepts, 7, 29–39.

    Article  PubMed  CAS  Google Scholar 

  70. Palumaa, P. (2013). Copper chaperones. The concept of conformational control in the metabolism of copper. FEBS Letters, 587, 1902–1910.

    Article  PubMed  CAS  Google Scholar 

  71. Festa, R. A., & Thiele, D. J. (2011). Copper: An essential metal in biology. Current Biology, 21, R877–R883.

    Article  PubMed  CAS  Google Scholar 

  72. Ackerman, C. M., & Chang, C. J. (2018). Copper signaling in the brain and beyond. The Journal of Biological Chemistry, 293, 4628–4635.

    Article  PubMed  CAS  Google Scholar 

  73. Öhrvik, H., & Thiele, D. J. (2015). The role of Ctr1 and Ctr2 in mammalian copper homeostasis and platinum-based chemotherapy. Journal of Trace Elements in Medicine and Biology, 31, 178–182.

    Article  PubMed  CAS  Google Scholar 

  74. Swaminath, G., Lee, T. W., & Kobilka, B. (2003). Identification of an allosteric binding site for Zn2+ on the beta2 adrenergic receptor. The Journal of Biological Chemistry, 278, 352–356.

    Article  PubMed  CAS  Google Scholar 

  75. Schetz, J. A., Chu, A., & Sibley, D. R. (1999). Zinc modulates antagonist interactions with D2-like dopamine receptors through distinct molecular mechanisms. The Journal of Pharmacology and Experimental Therapeutics, 289, 956–964.

    PubMed  CAS  Google Scholar 

  76. Elling, C. E., Nielsen, S. M., & Schwartz, T. W. (1995). Conversion of antagonist-binding site to metal-ion site in the tachykinin NK-1 receptor. Nature, 374, 74.

    Article  PubMed  CAS  Google Scholar 

  77. Thirstrup, K., Elling, C. E., Hjorth, S. A., et al. (1996). Construction of a high affinity zinc switch in the kappa-opioid receptor. The Journal of Biological Chemistry, 271, 7875–7878.

    Article  PubMed  CAS  Google Scholar 

  78. Rosenkilde, M. M., Lucibello, M., Holst, B., et al. (1998). Natural agonist enhancing bis-His zinc-site in transmembrane segment V of the tachykinin NK3 receptor. FEBS Letters, 439, 35–40.

    Article  PubMed  CAS  Google Scholar 

  79. Gaier, E. D., Eipper, B. A., & Mains, R. E. (2013). Copper signaling in the mammalian nervous system: Synaptic effects. Journal of Neuroscience Research, 91, 2–19.

    PubMed  CAS  Google Scholar 

  80. Calvo, D. J., & Beltran Gonzalez, A. N. (2016). Dynamic regulation of the GABAA receptor function by redox mechanisms. Molecular Pharmacology, 90, 326–333.

    Article  PubMed  CAS  Google Scholar 

  81. Calero, C. I., & Calvo, D. J. (2008). Redox modulation of homomeric rho1 GABA receptors. Journal of Neurochemistry, 105, 2367–2374.

    Article  PubMed  CAS  Google Scholar 

  82. Kowalik-Jankowska, T., Jankowska, Eb, & Kasprzykowski, F. (2010). Coordination abilities of a fragment containing D1 and H12 residues of neuropeptide γ and products of metal-catalyzed oxidation. Inorganic Chemistry, 49, 2182–2192.

    Article  PubMed  CAS  Google Scholar 

  83. Gajewska, A., Zielinska-Gorska, M., Wolinska-Witort, E., et al. (2016). Intracellular mechanisms involved in copper-gonadotropin-releasing hormone (Cu-GnRH) complex-induced cAMP/PKA signaling in female rat anterior pituitary cells in vitro. Brain Research Bulletin, 120, 75–82.

    Article  PubMed  CAS  Google Scholar 

  84. Shahzad, R., Jones, M. R., Viles, J. H., et al. (2016). Endocytosis of the tachykinin neuropeptide, neurokinin B, in astrocytes and its role in cellular copper uptake. Journal of Inorganic Biochemistry, 162, 319–325.

    Article  PubMed  CAS  Google Scholar 

  85. Jankowska, E., Błaszak, M., & Kowalik-Jankowska, T. (2013). Copper (II) complexes of neurokinin A with point mutation (S5A) and products of copper-catalyzed oxidation; role of serine residue in peptides containing neurokinin A sequence. Journal of Inorganic Biochemistry, 121, 1–9.

    Article  PubMed  CAS  Google Scholar 

  86. Gul, A. S., Tran, K. K., Jones, C. E., & Neurokinin (2018). B and serum albumin limit copper binding to mammalian gonadotropin releasing hormone. Biochemical and Biophysical Research Communications, 497, 1–6.

    Article  PubMed  CAS  Google Scholar 

  87. Jones, C. E., Zandawala, M., Semmens, D. C., et al. (2016). Identification of a neuropeptide precursor protein that gives rise to a “cocktail” of peptides that bind Cu(II) and generate metal-linked dimers. Biochimica et Biophysica Acta, 1860, 57–66.

    Article  PubMed  CAS  Google Scholar 

  88. Russino, D., McDonald, E., Hejazi, L., et al. (2013). The tachykinin peptide neurokinin B binds copper forming an unusual [CuII(NKB)2] complex and inhibits copper uptake into 1321N1 astrocytoma cells. ACS Chemical Neuroscience, 4, 1371–1381.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Zavitsanos, K., Nunes, A. M., Malandrinos, G., et al. (2011). Copper effective binding with 32-62 and 94-125 peptide fragments of histone H2B. Journal of Inorganic Biochemistry, 105, 102–110.

    Article  PubMed  CAS  Google Scholar 

  90. Ohrvik, H., & Wittung-Stafshede, P. (2015). Identification of new potential interaction partners for human cytoplasmic copper chaperone Atox1: Roles in gene regulation? International Journal of Molecular Sciences, 16, 16728–16739.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Lee, D. K., Lanca, A. J., Cheng, R., et al. (2004). Agonist-independent nuclear localization of the apelin, angiotensin AT1, and bradykinin B2 receptors. The Journal of Biological Chemistry, 279, 7901–7908.

    Article  PubMed  CAS  Google Scholar 

  92. Qin, K., Dong, C., Wu, G., et al. (2011). Inactive-state preassembly of G(q)-coupled receptors and G(q) heterotrimers. Nature Chemical Biology, 7, 740–747.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Lohse, M. J., Benovic, J. L., Codina, J., et al. (1990). beta-Arrestin: A protein that regulates beta-adrenergic receptor function. Science, 248, 1547–1550.

    Article  PubMed  CAS  Google Scholar 

  94. Erlandson, S. C., McMahon, C., and Kruse, A. C. (2018) Structural basis for G protein-coupled receptor signaling. Annual Review Biophysics

  95. Ohgami, R. S., Campagna, D. R., McDonald, A., et al. (2006). The Steap proteins are metalloreductases. Blood, 108, 1388–1394.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgements

RM acknowledges the financial support of Australian Rotary Health, the Rotary Club of Holroyd and Western Sydney University. The authors declare no conflicts of interest.

Author information

Author notes

    Authors and Affiliations

    1. School of Science and Health, Western Sydney University, Locked bag 1797, Sydney, 2153, New South Wales, Australia

      Katerina Christofides, Resmi Menon & Christopher E. Jones

    Authors
    1. Katerina Christofides
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Resmi Menon
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Christopher E. Jones
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Christopher E. Jones.

    Ethics declarations

    Conflict of Interest

    The authors declare that they have no conflict of interest.

    Additional information

    These authors contributed equally: Katerina Christofides, Resmi Menon.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Christofides, K., Menon, R. & Jones, C.E. Endocytosis of G Protein-Coupled Receptors and Their Ligands: Is There a Role in Metal Trafficking?. Cell Biochem Biophys 76, 329–337 (2018). https://doi.org/10.1007/s12013-018-0850-9

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s12013-018-0850-9

    Keywords

    Search

    Navigation