Home LiteratureArticle Details
PMID: 17848565 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Regulation of arrestin binding by rhodopsin phosphorylation level.

The Journal of biological chemistry ·Vol. 282 ·No. 44 ·2007-11-02 ·Pages 32075-83

Vishnivetskiy SA, Raman D, Wei J, Kennedy MJ, Hurley JB, Gurevich VV

Abstract

Arrestins ensure the timely termination of receptor signaling. The role of rhodopsin phosphorylation in visual arrestin binding was established more than 20 years ago, but the effects of the number of receptor-attached phosphates on this interaction remain controversial. Here we use purified rhodopsin fractions with carefully quantified content of individual phosphorylated rhodopsin species to elucidate the impact of phosphorylation level on arrestin interaction with three biologically relevant functional forms of rhodopsin: light-activated and dark phosphorhodopsin and phospho-opsin. We found that a single receptor-attached phosphate does not facilitate arrestin binding, two are necessary to induce high affinity interaction, and three phosphates fully activate arrestin. Higher phosphorylation levels do not increase the stability of arrestin complex with light-activated rhodopsin but enhance its binding to the dark phosphorhodopsin and phospho-opsin. The complex of arrestin with hyperphosphorylated light-activated rhodopsin is less sensitive to high salt and appears to release retinal faster. These data suggest that arrestin likely quenches rhodopsin signaling after the third phosphate is added by rhodopsin kinase. The complex of arrestin with heavily phosphorylated rhodopsin, which appears to form in certain disease states, has distinct characteristics that may contribute to the phenotype of these visual disorders.

MeSH Terms
Animals Arrestin/metabolism Binding Sites Cattle G-Protein-Coupled Receptor Kinase 1/metabolism Phosphorylation Retina/chemistry,metabolism Rhodopsin/isolation & purification,metabolism Vision, Ocular
Chemicals
Arrestin Rhodopsin G-Protein-Coupled Receptor Kinase 1
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Vishnivetskiy Sergey A
Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, USA.
Raman Dayanidhi
Wei Junhua
Kennedy Matthew J
Hurley James B
Gurevich Vsevolod V
References (75)
75 references, click to expand
  1. Targeted construction of phosphorylation-independent beta-arrestin mutants with constitutive activity in cells.
    J Biol Chem. 1999 Mar 12;274(11):6831-4 PMID: 10066734
  2. The differential engagement of arrestin surface charges by the various functional forms of the receptor.
    J Biol Chem. 2006 Feb 10;281(6):3458-62 PMID: 16339758
  3. How does arrestin respond to the phosphorylated state of rhodopsin?
    J Biol Chem. 1999 Apr 23;274(17):11451-4 PMID: 10206946
  4. Phosphorylation of non-bleached rhodopsin in intact retinas and living frogs.
    J Biol Chem. 1996 Aug 16;271(33):19826-30 PMID: 8702691
  5. Variability in the time course of single photon responses from toad rods: termination of rhodopsin's activity.
    Neuron. 1999 Jun;23(2):337-51 PMID: 10399939
  6. N-formyl peptide receptor phosphorylation domains differentially regulate arrestin and agonist affinity.
    J Biol Chem. 2003 Feb 7;278(6):4041-7 PMID: 12424254
  7. G-protein-coupled receptors: turn-ons and turn-offs.
    Curr Opin Neurobiol. 1998 Jun;8(3):335-44 PMID: 9687355
  8. Constitutive activation of opsin: interaction of mutants with rhodopsin kinase and arrestin.
    Biochemistry. 1995 Sep 19;34(37):11938-45 PMID: 7547930
  9. Origin of reproducibility in the responses of retinal rods to single photons.
    Biophys J. 1998 Oct;75(4):1836-57 PMID: 9746525
  10. Constitutive activation of phototransduction by K296E opsin is not a cause of photoreceptor degeneration.
    Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3551-5 PMID: 7724596
  11. Stable rhodopsin/arrestin complex leads to retinal degeneration in a transgenic mouse model of autosomal dominant retinitis pigmentosa.
    J Neurosci. 2006 Nov 15;26(46):11929-37 PMID: 17108167
  12. The structural basis of arrestin-mediated regulation of G-protein-coupled receptors.
    Pharmacol Ther. 2006 Jun;110(3):465-502 PMID: 16460808
  13. Multiple phosphorylation of rhodopsin and the in vivo chemistry underlying rod photoreceptor dark adaptation.
    Neuron. 2001 Jul 19;31(1):87-101 PMID: 11498053
  14. Molecular tinkering of G protein-coupled receptors: an evolutionary success.
    EMBO J. 1999 Apr 1;18(7):1723-9 PMID: 10202136
  15. Mapping the arrestin-receptor interface. Structural elements responsible for receptor specificity of arrestin proteins.
    J Biol Chem. 2004 Jan 9;279(2):1262-8 PMID: 14530255
  16. Rapid and reproducible deactivation of rhodopsin requires multiple phosphorylation sites.
    Neuron. 2000 Oct;28(1):153-64 PMID: 11086991
  17. Light causes phosphorylation of nonactivated visual pigments in intact mouse rod photoreceptor cells.
    J Biol Chem. 2005 Dec 16;280(50):41184-91 PMID: 16219764
  18. The 2.8 A crystal structure of visual arrestin: a model for arrestin's regulation.
    Cell. 1999 Apr 16;97(2):257-69 PMID: 10219246
  19. Light-dependent redistribution of arrestin in vertebrate rods is an energy-independent process governed by protein-protein interactions.
    Neuron. 2005 May 19;46(4):555-67 PMID: 15944125
  20. Functional antagonism of different G protein-coupled receptor kinases for beta-arrestin-mediated angiotensin II receptor signaling.
    Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1442-7 PMID: 15671181
  21. Duration and amplitude of the light-induced cGMP hydrolysis in vertebrate photoreceptors are regulated by multiple phosphorylation of rhodopsin and by arrestin binding.
    Biochemistry. 1995 Jan 31;34(4):1446-54 PMID: 7827093
  22. Crystal structure of cone arrestin at 2.3A: evolution of receptor specificity.
    J Mol Biol. 2005 Dec 16;354(5):1069-80 PMID: 16289201
  23. Use of bacteriophage RNA polymerase in RNA synthesis.
    Methods Enzymol. 1996;275:382-97 PMID: 9026651
  24. Phosphorylation modulates the affinity of light-activated rhodopsin for G protein and arrestin.
    Biochemistry. 2000 May 16;39(19):5738-49 PMID: 10801324
  25. Concentration-dependent tetramerization of bovine visual arrestin.
    Biophys J. 2003 Aug;85(2):1186-95 PMID: 12885662
  26. Visual pigment phosphorylation but not transducin translocation can contribute to light adaptation in zebrafish cones.
    Neuron. 2004 Mar 25;41(6):915-28 PMID: 15046724
  27. Each rhodopsin molecule binds its own arrestin.
    Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3125-8 PMID: 17360618
  28. RGS expression rate-limits recovery of rod photoresponses.
    Neuron. 2006 Aug 17;51(4):409-16 PMID: 16908407
  29. Mechanism of phosphorylation-recognition by visual arrestin and the transition of arrestin into a high affinity binding state.
    Mol Pharmacol. 1997 Jan;51(1):161-9 PMID: 9016359
  30. Arrestins: ubiquitous regulators of cellular signaling pathways.
    Genome Biol. 2006;7(9):236 PMID: 17020596
  31. The role of arrestin and retinoids in the regeneration pathway of rhodopsin.
    J Biol Chem. 1992 Aug 5;267(22):15701-6 PMID: 1386362
  32. Regulation of rhodopsin dephosphorylation by arrestin.
    J Biol Chem. 1989 Sep 25;264(27):15770-3 PMID: 2550422
  33. Phosphorylation of frog photoreceptor membranes induced by light.
    Nat New Biol. 1972 May 24;237(73):125-7 PMID: 4503852
  34. Rhodopsin phosphorylation and dephosphorylation in vivo.
    J Biol Chem. 1995 Jun 16;270(24):14259-62 PMID: 7782279
  35. Arrestin translocation is induced at a critical threshold of visual signaling and is superstoichiometric to bleached rhodopsin.
    J Neurosci. 2006 Jan 25;26(4):1146-53 PMID: 16436601
  36. Structure and function in rhodopsin: asymmetric reconstitution of rhodopsin in liposomes.
    Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13409-12 PMID: 12370420
  37. Arrestin with a single amino acid substitution quenches light-activated rhodopsin in a phosphorylation-independent fashion.
    Biochemistry. 1997 Jun 10;36(23):7058-63 PMID: 9188704
  38. Arrestin interactions with G protein-coupled receptors. Direct binding studies of wild type and mutant arrestins with rhodopsin, beta 2-adrenergic, and m2 muscarinic cholinergic receptors.
    J Biol Chem. 1995 Jan 13;270(2):720-31 PMID: 7822302
  39. Mechanism of quenching of phototransduction. Binding competition between arrestin and transducin for phosphorhodopsin.
    J Biol Chem. 1997 Jul 18;272(29):18125-31 PMID: 9218446
  40. Visual arrestin activity may be regulated by self-association.
    J Biol Chem. 1999 Jul 23;274(30):21186-90 PMID: 10409673
  41. Light induced shift and binding of S-antigen in retinal rods.
    Curr Eye Res. 1985 May;4(5):613-8 PMID: 2410196
  42. Light activation of one rhodopsin molecule causes the phosphorylation of hundreds of others. A reaction observed in electropermeabilized frog rod outer segments exposed to dim illumination.
    J Biol Chem. 1990 Sep 5;265(25):15333-40 PMID: 2394724
  43. Differential immunogold-dextran labeling of bovine and frog rod and cone cells using monoclonal antibodies against bovine rhodopsin.
    Exp Eye Res. 1986 Jan;42(1):55-71 PMID: 2420630
  44. Differential interaction of spin-labeled arrestin with inactive and active phosphorhodopsin.
    Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):4900-5 PMID: 16547131
  45. Structure and function of the visual arrestin oligomer.
    EMBO J. 2007 Mar 21;26(6):1726-36 PMID: 17332750
  46. An additional phosphate-binding element in arrestin molecule. Implications for the mechanism of arrestin activation.
    J Biol Chem. 2000 Dec 29;275(52):41049-57 PMID: 11024026
  47. Toward a unified model of vertebrate rod phototransduction.
    Vis Neurosci. 2005 Jul-Aug;22(4):417-36 PMID: 16212700
  48. Dynamics of arrestin-rhodopsin interactions: arrestin and retinal release are directly linked events.
    J Biol Chem. 2005 Feb 25;280(8):6861-71 PMID: 15591052
  49. Transduction of receptor signals by beta-arrestins.
    Science. 2005 Apr 22;308(5721):512-7 PMID: 15845844
  50. The nature of the arrestin x receptor complex determines the ultimate fate of the internalized receptor.
    J Biol Chem. 2003 Mar 28;278(13):11623-32 PMID: 12525498
  51. Visual arrestin binding to rhodopsin. Diverse functional roles of positively charged residues within the phosphorylation-recognition region of arrestin.
    J Biol Chem. 1995 Mar 17;270(11):6010-6 PMID: 7890732
  52. Rhodopsin phosphorylation in rats exposed to intense light.
    Photochem Photobiol. 2005 May-Jun;81(3):541-7 PMID: 15504085
  53. The selectivity of visual arrestin for light-activated phosphorhodopsin is controlled by multiple nonredundant mechanisms.
    J Biol Chem. 1998 Jun 19;273(25):15501-6 PMID: 9624137
  54. Transition of arrestin into the active receptor-binding state requires an extended interdomain hinge.
    J Biol Chem. 2002 Nov 15;277(46):43961-7 PMID: 12215448
  55. Control of rhodopsin multiple phosphorylation.
    Biochemistry. 1994 Feb 1;33(4):1023-8 PMID: 8305429
  56. Conservation of the phosphate-sensitive elements in the arrestin family of proteins.
    J Biol Chem. 2002 Mar 15;277(11):9043-8 PMID: 11782458
  57. Structural and functional impairment of endocytic pathways by retinitis pigmentosa mutant rhodopsin-arrestin complexes.
    J Clin Invest. 2004 Jul;114(1):131-40 PMID: 15232620
  58. A molecular pathway for light-dependent photoreceptor apoptosis in Drosophila.
    Neuron. 2000 Oct;28(1):139-52 PMID: 11086990
  59. Arrestin: mutagenesis, expression, purification, and functional characterization.
    Methods Enzymol. 2000;315:422-37 PMID: 10736718
  60. Visual and both non-visual arrestins in their "inactive" conformation bind JNK3 and Mdm2 and relocalize them from the nucleus to the cytoplasm.
    J Biol Chem. 2006 Jul 28;281(30):21491-9 PMID: 16737965
  61. The new face of active receptor bound arrestin attracts new partners.
    Structure. 2003 Sep;11(9):1037-42 PMID: 12962621
  62. Isolation of isoelectric species of phosphorylated rhodopsin.
    Methods Enzymol. 2000;315:70-6 PMID: 10736694
  63. Light dependent phosphorylation of rhodopsin by ATP.
    FEBS Lett. 1972 Jan 15;20(1):1-6 PMID: 11946367
  64. Mechanism of rhodopsin kinase activation.
    J Biol Chem. 1991 Jul 15;266(20):12949-55 PMID: 2071581
  65. Multiple phosphorylation sites confer reproducibility of the rod's single-photon responses.
    Science. 2006 Jul 28;313(5786):530-3 PMID: 16873665
  66. Agonist-receptor-arrestin, an alternative ternary complex with high agonist affinity.
    J Biol Chem. 1997 Nov 14;272(46):28849-52 PMID: 9360951
  67. Cell-free expression of visual arrestin. Truncation mutagenesis identifies multiple domains involved in rhodopsin interaction.
    J Biol Chem. 1992 Oct 25;267(30):21919-23 PMID: 1400502
  68. The formation of stable rhodopsin-arrestin complexes induces apoptosis and photoreceptor cell degeneration.
    Neuron. 2000 Oct;28(1):129-38 PMID: 11086989
  69. Different G protein-coupled receptor kinases govern G protein and beta-arrestin-mediated signaling of V2 vasopressin receptor.
    Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1448-53 PMID: 15671180
  70. Light-induced binding of 48-kDa protein to photoreceptor membranes is highly enhanced by phosphorylation of rhodopsin.
    FEBS Lett. 1984 Oct 29;176(2):473-8 PMID: 6436059
  71. Light-dependent phosphorylation of rhodopsin: number of phosphorylation sites.
    Biochemistry. 1982 Jun 8;21(12):3014-22 PMID: 6980670
  72. Determinants of single photon response variability.
    J Gen Physiol. 1994 Apr;103(4):679-90 PMID: 8057084
  73. Visual arrestin interaction with rhodopsin. Sequential multisite binding ensures strict selectivity toward light-activated phosphorylated rhodopsin.
    J Biol Chem. 1993 Jun 5;268(16):11628-38 PMID: 8505295
  74. Crystal structure of beta-arrestin at 1.9 A: possible mechanism of receptor binding and membrane Translocation.
    Structure. 2001 Sep;9(9):869-80 PMID: 11566136
  75. Mass spectrometric analysis of the kinetics of in vivo rhodopsin phosphorylation.
    Protein Sci. 2002 Apr;11(4):862-74 PMID: 11910029
Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
0021-9258
DOI
10.1074/jbc.M706057200
Published
2007-11-02
Epub
2007-00-11
Pages
32075-83
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC2638115
Subset
IM
Grants
NEI NIH HHS · R01 EY006641 · United States
NEI NIH HHS · F32 EY006641 · United States
NEI NIH HHS · R01 EY006641-22 · United States
NEI NIH HHS · EY06641 · United States
NEI NIH HHS · EY11500 · United States
NEI NIH HHS · R01 EY011500-12 · United States
NEI NIH HHS · R01 EY011500 · United States
External Links
PubMed source DOI: 10.1074/jbc.M706057200 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2