Advertisement

The Journal of Membrane Biology

, Volume 252, Issue 4–5, pp 413–423 | Cite as

Rhodopsin Oligomerization and Aggregation

  • Paul S.-H. ParkEmail author
Article
  • 198 Downloads
Part of the following topical collections:
  1. Membrane and Receptor Dynamics

Abstract

Rhodopsin is the light receptor in photoreceptor cells of the retina and a prototypical G protein-coupled receptor. Two types of quaternary structures can be adopted by rhodopsin. If rhodopsin folds and attains a proper tertiary structure, it can then form oligomers and nanodomains within the photoreceptor cell membrane. In contrast, if rhodopsin misfolds, it cannot progress through the biosynthetic pathway and instead will form aggregates that can cause retinal degenerative disease. In this review, emerging views are highlighted on the supramolecular organization of rhodopsin within the membrane of photoreceptor cells and the aggregation of rhodopsin that can lead to retinal degeneration.

Keywords

G protein-coupled receptor Quaternary structure Photoreceptor cell Retina Phototransduction Retinal degeneration 

Notes

Funding

This work was funded by a Grant from the National Institutes of Health (R01EY021731).

Compliance with Ethical Standards

Conflict of interest

The author declares that he has no conflicts of interest to disclose.

Ethical Approval

This article does not contain any studies with human participants or animals performed by the author.

References

  1. Adekeye A, Haeri M, Solessio E, Knox BE (2014) Ablation of the proapoptotic genes CHOP or Ask1 does not prevent or delay loss of visual function in a P23H transgenic mouse model of retinitis pigmentosa. PLoS ONE 9:e83871.  https://doi.org/10.1371/journal.pone.0083871 CrossRefPubMedPubMedCentralGoogle Scholar
  2. Albert AD, Young JE, Paw Z (1998) Phospholipid fatty acyl spatial distribution in bovine rod outer segment disk membranes. Biochim Biophys Acta 1368:52–60CrossRefGoogle Scholar
  3. Andrews LD, Cohen AI (1979) Freeze-fracture evidence for the presence of cholesterol in particle-free patches of basal disks and the plasma membrane of retinal rod outer segments of mice and frogs. J Cell Biol 81:215–228CrossRefGoogle Scholar
  4. Arango-Gonzalez B et al (2014) Identification of a common non-apoptotic cell death mechanism in hereditary retinal degeneration. PLoS ONE 9:e112142.  https://doi.org/10.1371/journal.pone.0112142 CrossRefPubMedPubMedCentralGoogle Scholar
  5. Athanasiou D et al (2012) BiP prevents rod opsin aggregation. Mol Biol Cell 23:3522–3531.  https://doi.org/10.1091/mbc.e12-02-0168 CrossRefPubMedPubMedCentralGoogle Scholar
  6. Athanasiou D, Aguila M, Bevilacqua D, Novoselov SS, Parfitt DA, Cheetham ME (2013) The cell stress machinery and retinal degeneration. FEBS Lett 587:2008–2017.  https://doi.org/10.1016/j.febslet.2013.05.020 CrossRefPubMedPubMedCentralGoogle Scholar
  7. Athanasiou D, Aguila M, Bellingham J, Li W, McCulley C, Reeves PJ, Cheetham ME (2018) The molecular and cellular basis of rhodopsin retinitis pigmentosa reveals potential strategies for therapy. Prog Retin Eye Res 62:1–23.  https://doi.org/10.1016/j.preteyeres.2017.10.002 CrossRefPubMedGoogle Scholar
  8. Baylor DA, Lamb TD (1982) Local effects of bleaching in retinal rods of the toad. J Physiol 328:49–71CrossRefGoogle Scholar
  9. Baylor DA, Lamb TD, Yau KW (1979) Responses of retinal rods to single photons. J Physiol 288:613–634PubMedPubMedCentralGoogle Scholar
  10. Beerepoot P, Nazari R, Salahpour A (2017) Pharmacological chaperone approaches for rescuing GPCR mutants: current state, challenges, and screening strategies. Pharmacol Res 117:242–251.  https://doi.org/10.1016/j.phrs.2016.12.036 CrossRefPubMedGoogle Scholar
  11. Bence NF, Sampat RM, Kopito RR (2001) Impairment of the ubiquitin-proteasome system by protein aggregation. Science 292:1552–1555.  https://doi.org/10.1126/science.292.5521.1552 CrossRefPubMedPubMedCentralGoogle Scholar
  12. Bethani I, Skanland SS, Dikic I, Acker-Palmer A (2010) Spatial organization of transmembrane receptor signalling. EMBO J 29:2677–2688.  https://doi.org/10.1038/emboj.2010.175 CrossRefPubMedPubMedCentralGoogle Scholar
  13. Boesze-Battaglia K, Albert AD (1989) Fatty acid composition of bovine rod outer segment plasma membrane. Exp Eye Res 49:699–701CrossRefGoogle Scholar
  14. Boesze-Battaglia K, Fliesler SJ, Albert AD (1990) Relationship of cholesterol content to spatial distribution and age of disc membranes in retinal rod outer segments. J Biol Chem 265:18867–18870PubMedPubMedCentralGoogle Scholar
  15. Botelho AV, Huber T, Sakmar TP, Brown MF (2006) Curvature and hydrophobic forces drive oligomerization and modulate activity of rhodopsin in membranes. Biophys J 91:4464–4477.  https://doi.org/10.1529/biophysj.106.082776 CrossRefPubMedPubMedCentralGoogle Scholar
  16. Brown MF (1994) Modulation of rhodopsin function by properties of the membrane bilayer. Chem Phys Lipids 73:159–180CrossRefGoogle Scholar
  17. Bush RA, Malnoe A, Reme CE, Williams TP (1994) Dietary deficiency of N-3 fatty acids alters rhodopsin content and function in the rat retina. Invest Ophthalmol Vis Sci 35:91–100PubMedGoogle Scholar
  18. Caldwell RB, McLaughlin BJ (1985) Freeze-fracture study of filipin binding in photoreceptor outer segments and pigment epithelium of dystrophic and normal retinas. J Comp Neurol 236:523–537.  https://doi.org/10.1002/cne.902360408 CrossRefPubMedGoogle Scholar
  19. Calebiro D et al (2013) Single-molecule analysis of fluorescently labeled G-protein-coupled receptors reveals complexes with distinct dynamics and organization. Proc Natl Acad Sci USA 110:743–748.  https://doi.org/10.1073/pnas.1205798110 CrossRefPubMedGoogle Scholar
  20. Cangiano L, Dell’Orco D (2013) Detecting single photons: a supramolecular matter? FEBS Lett 587:1–4.  https://doi.org/10.1016/j.febslet.2012.11.015 CrossRefPubMedGoogle Scholar
  21. Chabre M, le Maire M (2005) Monomeric G-protein-coupled receptor as a functional unit. Biochemistry 44:9395–9403CrossRefGoogle Scholar
  22. Chabre M, Cone R, Saibil H (2003) Biophysics: is rhodopsin dimeric in native retinal rods? Nature 426:30–31CrossRefGoogle Scholar
  23. Chen Y et al (2014) Inherent instability of the retinitis pigmentosa P23H mutant opsin. J Biol Chem 289:9288–9303.  https://doi.org/10.1074/jbc.m114.551713 CrossRefPubMedPubMedCentralGoogle Scholar
  24. Chen Y, Tang H, Seibel W, Papoian R, Li X, Lambert NA, Palczewski K (2015) A high-throughput drug screening strategy for detecting rhodopsin P23H mutant rescue and degradation. Invest Ophthalmol Vis Sci 56:2553–2567.  https://doi.org/10.1167/iovs.14-16298 CrossRefPubMedPubMedCentralGoogle Scholar
  25. Chiang WC et al (2014) Robust endoplasmic reticulum-associated degradation of rhodopsin precedes retinal degeneration. Mol Neurobiol.  https://doi.org/10.1007/s12035-014-8881-8 CrossRefPubMedPubMedCentralGoogle Scholar
  26. Chiti F, Dobson CM (2006) Protein misfolding, functional amyloid, and human disease. Annu Rev Biochem 75:333–366.  https://doi.org/10.1146/annurev.biochem.75.101304.123901 CrossRefPubMedGoogle Scholar
  27. Comar WD, Schubert SM, Jastrzebska B, Palczewski K, Smith AW (2014) Time-resolved fluorescence spectroscopy measures clustering and mobility of a G protein-coupled receptor opsin in live cell membranes. J Am Chem Soc 136:8342–8349.  https://doi.org/10.1021/ja501948w CrossRefPubMedPubMedCentralGoogle Scholar
  28. Daemen FJ (1973) Vertebrate rod outer segment membranes. Biochim Biophys Acta 300:255–288CrossRefGoogle Scholar
  29. Dalke C, Graw J (2005) Mouse mutants as models for congenital retinal disorders. Exp Eye Res 81:503–512CrossRefGoogle Scholar
  30. Dell’Orco D (2013) A physiological role for the supramolecular organization of rhodopsin and transducin in rod photoreceptors. FEBS Lett 587:2060–2066.  https://doi.org/10.1016/j.febslet.2013.05.017 CrossRefPubMedGoogle Scholar
  31. Dell’Orco D, Schmidt H (2008) Mesoscopic Monte Carlo simulations of stochastic encounters between photoactivated rhodopsin and transducin in disc membranes. J Phys Chem B 112:4419–4426CrossRefGoogle Scholar
  32. Ding JD, Salinas RY, Arshavsky VY (2015) Discs of mammalian rod photoreceptors form through the membrane evagination mechanism. J Cell Biol 211:495–502.  https://doi.org/10.1083/jcb.201508093 CrossRefPubMedPubMedCentralGoogle Scholar
  33. Dryja TP et al (1990) A point mutation of the rhodopsin gene in one form of retinitis pigmentosa. Nature 343:364–366.  https://doi.org/10.1038/343364a0 CrossRefPubMedGoogle Scholar
  34. Garriga P, Liu X, Khorana HG (1996) Structure and function in rhodopsin: correct folding and misfolding in point mutants at and in proximity to the site of the retinitis pigmentosa mutation Leu-125→Arg in the transmembrane helix C. Proc Natl Acad Sci USA 93:4560–4564CrossRefGoogle Scholar
  35. Gilliam JC et al (2012) Three-dimensional architecture of the rod sensory cilium and its disruption in retinal neurodegeneration. Cell 151:1029–1041.  https://doi.org/10.1016/j.cell.2012.10.038 CrossRefPubMedPubMedCentralGoogle Scholar
  36. Goldberg AF, Moritz OL, Williams DS (2016) Molecular basis for photoreceptor outer segment architecture. Prog Retin Eye Res 55:52–81.  https://doi.org/10.1016/j.preteyeres.2016.05.003 CrossRefPubMedPubMedCentralGoogle Scholar
  37. Gorbatyuk M, Gorbatyuk O (2013) Review: retinal degeneration: focus on the unfolded protein response. Mol Vis 19:1985–1998PubMedPubMedCentralGoogle Scholar
  38. Gorbatyuk MS et al (2010) Restoration of visual function in P23H rhodopsin transgenic rats by gene delivery of BiP/Grp78. Proc Natl Acad Sci USA 107:5961–5966.  https://doi.org/10.1073/pnas.0911991107 CrossRefPubMedGoogle Scholar
  39. Gragg M, Park PS (2018) Misfolded rhodopsin mutants display variable aggregation properties. Biochim Biophys Acta 1864:2938–2948.  https://doi.org/10.1016/j.bbadis.2018.06.004 CrossRefPubMedCentralGoogle Scholar
  40. Gragg M, Park PS (2019) Detection of misfolded rhodopsin aggregates in cells by Forster resonance energy transfer. Methods Cell Biol 149:87–105.  https://doi.org/10.1016/bs.mcb.2018.08.007 CrossRefPubMedGoogle Scholar
  41. Gragg M, Kim TG, Howell S, Park PS (2016) Wild-type opsin does not aggregate with a misfolded opsin mutant. Biochim Biophys Acta 1858:1850–1859.  https://doi.org/10.1016/j.bbamem.2016.04.013 CrossRefPubMedPubMedCentralGoogle Scholar
  42. Griciuc A, Aron L, Ueffing M (2011) ER stress in retinal degeneration: a target for rational therapy? Trends Mol Med 17:442–451.  https://doi.org/10.1016/j.molmed.2011.04.002 CrossRefPubMedGoogle Scholar
  43. Grossfield A, Feller SE, Pitman MC (2006) A role for direct interactions in the modulation of rhodopsin by omega-3 polyunsaturated lipids. Proc Natl Acad Sci USA 103:4888–4893.  https://doi.org/10.1073/pnas.0508352103 CrossRefPubMedGoogle Scholar
  44. Gunkel M, Schoneberg J, Alkhaldi W, Irsen S, Noe F, Kaupp UB, Al-Amoudi A (2015) Higher-order architecture of rhodopsin in intact photoreceptors and its implication for phototransduction kinetics. Structure 23:628–638.  https://doi.org/10.1016/j.str.2015.01.015 CrossRefPubMedGoogle Scholar
  45. Haeri M, Calvert PD, Solessio E, Pugh EN Jr, Knox BE (2013) Regulation of rhodopsin-eGFP distribution in transgenic xenopus rod outer segments by light. PLoS ONE 8:e80059.  https://doi.org/10.1371/journal.pone.0080059 CrossRefPubMedPubMedCentralGoogle Scholar
  46. Hartong DT, Berson EL, Dryja TP (2006) Retinitis pigmentosa. Lancet 368:1795–1809.  https://doi.org/10.1016/S0140-6736(06)69740-7 CrossRefPubMedGoogle Scholar
  47. Hegener O, Prenner L, Runkel F, Baader SL, Kappler J, Haberlein H (2004) Dynamics of beta2-adrenergic receptor-ligand complexes on living cells. Biochemistry 43:6190–6199.  https://doi.org/10.1021/bi035928t CrossRefPubMedGoogle Scholar
  48. Hern JA et al (2010) Formation and dissociation of M1 muscarinic receptor dimers seen by total internal reflection fluorescence imaging of single molecules. Proc Natl Acad Sci USA 107:2693–2698.  https://doi.org/10.1073/pnas.0907915107 CrossRefPubMedGoogle Scholar
  49. Herrick-Davis K, Grinde E, Lindsley T, Teitler M, Mancia F, Cowan A, Mazurkiewicz JE (2015) Native serotonin 5-HT2C receptors are expressed as homodimers on the apical surface of choroid plexus epithelial cells. Mol Pharmacol 87:660–673.  https://doi.org/10.1124/mol.114.096636 CrossRefPubMedPubMedCentralGoogle Scholar
  50. Hsu YC, Chuang JZ, Sung CH (2015) Light regulates the ciliary protein transport and outer segment disc renewal of Mammalian photoreceptors. Dev Cell 32:731–742.  https://doi.org/10.1016/j.devcel.2015.01.027 CrossRefPubMedPubMedCentralGoogle Scholar
  51. Hwa J, Garriga P, Liu X, Khorana HG (1997) Structure and function in rhodopsin: packing of the helices in the transmembrane domain and folding to a tertiary structure in the intradiscal domain are coupled. Proc Natl Acad Sci USA 94:10571–10576CrossRefGoogle Scholar
  52. Illing ME, Rajan RS, Bence NF, Kopito RR (2002) A rhodopsin mutant linked to autosomal dominant retinitis pigmentosa is prone to aggregate and interacts with the ubiquitin proteasome system. J Biol Chem 277:34150–34160CrossRefGoogle Scholar
  53. Insinna C, Besharse JC (2008) Intraflagellar transport and the sensory outer segment of vertebrate photoreceptors. Dev Dyn 237:1982–1992.  https://doi.org/10.1002/dvdy.21554 CrossRefPubMedPubMedCentralGoogle Scholar
  54. Jastrzebska B et al (2004) Functional characterization of rhodopsin monomers and dimers in detergents. J Biol Chem 279:54663–54675CrossRefGoogle Scholar
  55. Jastrzebska B, Fotiadis D, Jang GF, Stenkamp RE, Engel A, Palczewski K (2006) Functional and structural characterization of rhodopsin oligomers. J Biol Chem 281:11917–11922CrossRefGoogle Scholar
  56. Kasai RS, Suzuki KG, Prossnitz ER, Koyama-Honda I, Nakada C, Fujiwara TK, Kusumi A (2011) Full characterization of GPCR monomer-dimer dynamic equilibrium by single molecule imaging. J Cell Biol 192:463–480.  https://doi.org/10.1083/jcb.201009128 CrossRefPubMedPubMedCentralGoogle Scholar
  57. Kaushal S, Khorana HG (1994) Structure and function in rhodopsin. 7. Point mutations associated with autosomal dominant retinitis pigmentosa. Biochemistry 33:6121–6128CrossRefGoogle Scholar
  58. Kirchhoff H (2014) Diffusion of molecules and macromolecules in thylakoid membranes. Biochim Biophys Acta 1837:495–502.  https://doi.org/10.1016/j.bbabio.2013.11.003 CrossRefPubMedGoogle Scholar
  59. Knowles TP, Vendruscolo M, Dobson CM (2014) The amyloid state and its association with protein misfolding diseases. Nat Rev Mol Cell Biol 15:384–396.  https://doi.org/10.1038/nrm3810 CrossRefPubMedGoogle Scholar
  60. Kopito RR (2000) Aggresomes, inclusion bodies and protein aggregation. Trends Cell Biol 10:524–530CrossRefGoogle Scholar
  61. Krebs MP, Holden DC, Joshi P, Clark CL 3rd, Lee AH, Kaushal S (2010) Molecular mechanisms of rhodopsin retinitis pigmentosa and the efficacy of pharmacological rescue. J Mol Biol 395:1063–1078.  https://doi.org/10.1016/j.jmb.2009.11.015 CrossRefPubMedGoogle Scholar
  62. Kroeger H, Chiang WC, Lin JH (2012) Endoplasmic reticulum-associated degradation (ERAD) of misfolded glycoproteins and mutant P23H rhodopsin in photoreceptor cells. Adv Exp Med Biol 723:559–565.  https://doi.org/10.1007/978-1-4614-0631-0_71 CrossRefPubMedPubMedCentralGoogle Scholar
  63. Liang Y, Fotiadis D, Filipek S, Saperstein DA, Palczewski K, Engel A (2003) Organization of the G protein-coupled receptors rhodopsin and opsin in native membranes. J Biol Chem 278:21655–21662CrossRefGoogle Scholar
  64. Liu X, Garriga P, Khorana HG (1996) Structure and function in rhodopsin: correct folding and misfolding in two point mutants in the intradiscal domain of rhodopsin identified in retinitis pigmentosa. Proc Natl Acad Sci USA 93:4554–4559CrossRefGoogle Scholar
  65. Makino CL, Howard LN, Williams TP (1990) Axial gradients of rhodopsin in light-exposed retinal rods of the toad. J Gen Physiol 96:1199–1220CrossRefGoogle Scholar
  66. Mazzolini M et al (2015) The phototransduction machinery in the rod outer segment has a strong efficacy gradient. Proc Natl Acad Sci USA 112:E2715–E2724.  https://doi.org/10.1073/pnas.1423162112 CrossRefPubMedGoogle Scholar
  67. Mendes HF, Cheetham ME (2008) Pharmacological manipulation of gain-of-function and dominant-negative mechanisms in rhodopsin retinitis pigmentosa. Hum Mol Genet 17:3043–3054.  https://doi.org/10.1093/hmg/ddn202 CrossRefPubMedGoogle Scholar
  68. Mendes HF, van der Spuy J, Chapple JP, Cheetham ME (2005) Mechanisms of cell death in rhodopsin retinitis pigmentosa: implications for therapy. Trends Mol Med 11:177–185.  https://doi.org/10.1016/j.molmed.2005.02.007 CrossRefPubMedGoogle Scholar
  69. Miller LM, Gragg M, Kim TG, Park PS (2015) Misfolded opsin mutants display elevated beta-sheet structure. FEBS Lett 589:3119–3125.  https://doi.org/10.1016/j.febslet.2015.08.042 CrossRefPubMedPubMedCentralGoogle Scholar
  70. Mishra AK et al (2016) Quaternary structures of opsin in live cells revealed by FRET spectrometry. Biochem J 473:3819–3836.  https://doi.org/10.1042/bcj20160422 CrossRefPubMedPubMedCentralGoogle Scholar
  71. Mitchell DC, Niu SL, Litman BJ (2001) Optimization of receptor-G protein coupling by bilayer lipid composition I: kinetics of rhodopsin-transducin binding. J Biol Chem 276:42801–42806.  https://doi.org/10.1074/jbc.m105772200 CrossRefPubMedGoogle Scholar
  72. Mugler A, Tostevin F, ten Wolde PR (2013) Spatial partitioning improves the reliability of biochemical signaling. Proc Natl Acad Sci USA 110:5927–5932.  https://doi.org/10.1073/pnas.1218301110 CrossRefPubMedGoogle Scholar
  73. Muller DJ (2008) AFM: a nanotool in membrane biology. Biochemistry 47:7986–7998.  https://doi.org/10.1021/bi800753x CrossRefPubMedGoogle Scholar
  74. Nathans J, Merbs SL, Sung CH, Weitz CJ, Wang Y (1992) Molecular genetics of human visual pigments. Annu Rev Genet 26:403–424.  https://doi.org/10.1146/annurev.ge.26.120192.002155 CrossRefPubMedGoogle Scholar
  75. Nemet I, Ropelewski P, Imanishi Y (2015) Rhodopsin trafficking and mistrafficking: signals, molecular components, and mechanisms. Prog Mol Biol Transl Sci 132:39–71.  https://doi.org/10.1016/bs.pmbts.2015.02.007 CrossRefPubMedGoogle Scholar
  76. Nickell S, Park PS, Baumeister W, Palczewski K (2007) Three-dimensional architecture of murine rod outer segments determined by cryoelectron tomography. J Cell Biol 177:917–925CrossRefGoogle Scholar
  77. Niu SL, Mitchell DC, Litman BJ (2001) Optimization of receptor-G protein coupling by bilayer lipid composition II: formation of metarhodopsin II-transducin complex. J Biol Chem 276:42807–42811.  https://doi.org/10.1074/jbc.m105778200 CrossRefPubMedGoogle Scholar
  78. Niu SL, Mitchell DC, Lim SY, Wen ZM, Kim HY, Salem N Jr, Litman BJ (2004) Reduced G protein-coupled signaling efficiency in retinal rod outer segments in response to n-3 fatty acid deficiency. J Biol Chem 279:31098–31104.  https://doi.org/10.1074/jbc.m404376200 CrossRefPubMedGoogle Scholar
  79. Noorwez SM, Malhotra R, McDowell JH, Smith KA, Krebs MP, Kaushal S (2004) Retinoids assist the cellular folding of the autosomal dominant retinitis pigmentosa opsin mutant P23H. J Biol Chem 279:16278–16284CrossRefGoogle Scholar
  80. Opefi CA, South K, Reynolds CA, Smith SO, Reeves PJ (2013) Retinitis pigmentosa mutants provide insight into the role of the N-terminal cap in rhodopsin folding, structure, and function. J Biol Chem 288:33912–33926.  https://doi.org/10.1074/jbc.m113.483032 CrossRefPubMedPubMedCentralGoogle Scholar
  81. Organisciak DT, Noell WK (1977) The rod outer segment phospholipid/opsin ratio of rats maintained in darkness or cyclic light. Invest Ophthalmol Vis Sci 16:188–190PubMedGoogle Scholar
  82. Parfitt DA et al (2014) The heat-shock response co-inducer arimoclomol protects against retinal degeneration in rhodopsin retinitis pigmentosa. Cell Death Dis 5:e1236.  https://doi.org/10.1038/cddis.2014.214 CrossRefPubMedPubMedCentralGoogle Scholar
  83. Park PS (2014) Constitutively active rhodopsin and retinal disease. Adv Pharmacol 70:1–36.  https://doi.org/10.1016/b978-0-12-417197-8.00001-8 CrossRefPubMedPubMedCentralGoogle Scholar
  84. Patowary S, Alvarez-Curto E, Xu TR, Holz JD, Oliver JA, Milligan G, Raicu V (2013) The muscarinic M3 acetylcholine receptor exists as two differently sized complexes at the plasma membrane. Biochem J 452:303–312.  https://doi.org/10.1042/bj20121902 CrossRefPubMedGoogle Scholar
  85. Penn JS, Anderson RE (1987) Effect of light history on rod outer-segment membrane composition in the rat. Exp Eye Res 44:767–778CrossRefGoogle Scholar
  86. Periole X, Huber T, Marrink SJ, Sakmar TP (2007) G protein-coupled receptors self-assemble in dynamics simulations of model bilayers. J Am Chem Soc 129:10126–10132.  https://doi.org/10.1021/ja0706246 CrossRefPubMedGoogle Scholar
  87. Price BA, Sandoval IM, Chan F, Simons DL, Wu SM, Wensel TG, Wilson JH (2011) Mislocalization and degradation of human P23H-rhodopsin-GFP in a knockin mouse model of retinitis pigmentosa. Invest Ophthalmol Vis Sci 52:9728–9736.  https://doi.org/10.1167/iovs.11-8654 CrossRefPubMedPubMedCentralGoogle Scholar
  88. Radhakrishnan K, Halasz A, McCabe MM, Edwards JS, Wilson BS (2012) Mathematical simulation of membrane protein clustering for efficient signal transduction. Ann Biomed Eng 40:2307–2318.  https://doi.org/10.1007/s10439-012-0599-z CrossRefPubMedGoogle Scholar
  89. Rajan RS, Illing ME, Bence NF, Kopito RR (2001) Specificity in intracellular protein aggregation and inclusion body formation. Proc Natl Acad Sci USA 98:13060–13065.  https://doi.org/10.1073/pnas.181479798 CrossRefPubMedGoogle Scholar
  90. Rakshit T, Park PS (2015) Impact of reduced rhodopsin expression on the structure of rod outer segment disc membranes. Biochemistry 54:2885–2894.  https://doi.org/10.1021/acs.biochem.5b00003 CrossRefPubMedPubMedCentralGoogle Scholar
  91. Rakshit T, Senapati S, Sinha S, Whited AM, Park PS-H (2015) Rhodopsin forms nanodomains in rod outer segment disc membranes of the cold-blooded Xenopus laevis. PLoS ONE 10:e0141114CrossRefGoogle Scholar
  92. Rakshit T, Senapati S, Parmar VM, Sahu B, Maeda A, Park PS (2017) Adaptations in rod outer segment disc membranes in response to environmental lighting conditions. Biochim Biophys Acta 1864:1691–1702.  https://doi.org/10.1016/j.bbamcr.2017.06.013 CrossRefPubMedCentralGoogle Scholar
  93. Sakami S et al (2011) Probing mechanisms of photoreceptor degeneration in a new mouse model of the common form of autosomal dominant retinitis pigmentosa due to P23H opsin mutations. J Biol Chem 286:10551–10567.  https://doi.org/10.1074/jbc.m1 CrossRefPubMedPubMedCentralGoogle Scholar
  94. Saliba RS, Munro PM, Luthert PJ, Cheetham ME (2002) The cellular fate of mutant rhodopsin: quality control, degradation and aggresome formation. J Cell Sci 115:2907–2918PubMedGoogle Scholar
  95. Saxton MJ, Owicki JC (1989) Concentration effects on reactions in membranes: rhodopsin and transducin. Biochim Biophys Acta 979:27–34CrossRefGoogle Scholar
  96. Schoneberg J, Heck M, Hofmann KP, Noe F (2014) Explicit spatiotemporal simulation of receptor-g protein coupling in rod cell disk membranes. Biophys J 107:1042–1053.  https://doi.org/10.1016/j.bpj.2014.05.050 CrossRefPubMedPubMedCentralGoogle Scholar
  97. Senapati S, Park PS (2019) Investigating the nanodomain organization of rhodopsin in native membranes by atomic force microscopy. Methods Mol Biol 1886:61–74.  https://doi.org/10.1007/978-1-4939-8894-5_4 CrossRefPubMedGoogle Scholar
  98. Senapati S, Gragg M, Samuels IS, Parmar VM, Maeda A, Park PS (2018) Effect of dietary docosahexaenoic acid on rhodopsin content and packing in photoreceptor cell membranes. Biochim Biophys Acta 1860:1403–1413.  https://doi.org/10.1016/j.bbamem.2018.03.030 CrossRefPubMedCentralGoogle Scholar
  99. Sizova OS, Shinde VM, Lenox AR, Gorbatyuk MS (2014) Modulation of cellular signaling pathways in P23H rhodopsin photoreceptors. Cell Signal 26:665–672.  https://doi.org/10.1016/j.cellsig.2013.12.008 CrossRefPubMedGoogle Scholar
  100. Soubias O, Teague WE Jr, Hines KG, Gawrisch K (2015) Rhodopsin/lipid hydrophobic matching-rhodopsin oligomerization and function. Biophys J 108:1125–1132.  https://doi.org/10.1016/j.bpj.2015.01.006 CrossRefPubMedPubMedCentralGoogle Scholar
  101. Stojanovic A, Hwa J (2002) Rhodopsin and retinitis pigmentosa: shedding light on structure and function. Receptors Channels 8:33–50PubMedGoogle Scholar
  102. Stoneman MR, Paprocki JD, Biener G, Yokoi K, Shevade A, Kuchin S, Raicu V (2017) Quaternary structure of the yeast pheromone receptor Ste2 in living cells. Biochim Biophys Acta Biomembr 1859:1456–1464.  https://doi.org/10.1016/j.bbamem.2016.12.008 CrossRefPubMedGoogle Scholar
  103. Sung CH, Chuang JZ (2010) The cell biology of vision. J Cell Biol 190:953–963.  https://doi.org/10.1083/jcb.201006020 CrossRefPubMedPubMedCentralGoogle Scholar
  104. Sung CH et al (1991a) Rhodopsin mutations in autosomal dominant retinitis pigmentosa. Proc Natl Acad Sci USA 88:6481–6485CrossRefGoogle Scholar
  105. Sung CH, Schneider BG, Agarwal N, Papermaster DS, Nathans J (1991b) Functional heterogeneity of mutant rhodopsins responsible for autosomal dominant retinitis pigmentosa. Proc Natl Acad Sci USA 88:8840–8844CrossRefGoogle Scholar
  106. Sung CH, Davenport CM, Nathans J (1993) Rhodopsin mutations responsible for autosomal dominant retinitis pigmentosa. Clustering of functional classes along the polypeptide chain. J Biol Chem 268:26645–26649PubMedGoogle Scholar
  107. Tao YX, Conn PM (2014) Chaperoning G protein-coupled receptors: from cell biology to therapeutics. Endocr Rev 35:602–647.  https://doi.org/10.1210/er.2013-1121 CrossRefPubMedPubMedCentralGoogle Scholar
  108. Vasireddy V et al (2011) Rescue of photoreceptor degeneration by curcumin in transgenic rats with P23H rhodopsin mutation. PLoS ONE 6:e21193.  https://doi.org/10.1371/journal.pone.0021193 CrossRefPubMedPubMedCentralGoogle Scholar
  109. Volland S et al (2015) Three-dimensional organization of nascent rod outer segment disk membranes. Proc Natl Acad Sci USA 112:14870–14875.  https://doi.org/10.1073/pnas.1516309112 CrossRefPubMedGoogle Scholar
  110. Walter P, Ron D (2011) The unfolded protein response: from stress pathway to homeostatic regulation. Science 334:1081–1086.  https://doi.org/10.1126/science.1209038 CrossRefPubMedPubMedCentralGoogle Scholar
  111. Wang J, Deretic D (2014) Molecular complexes that direct rhodopsin transport to primary cilia. Prog Retin Eye Res 38:1–19.  https://doi.org/10.1016/j.preteyeres.2013.08.004 CrossRefPubMedGoogle Scholar
  112. Ward RJ, Pediani JD, Godin AG, Milligan G (2015) Regulation of oligomeric organization of the serotonin 5-hydroxytryptamine 2C (5-HT2C) receptor observed by spatial intensity distribution analysis. J Biol Chem 290:12844–12857.  https://doi.org/10.1074/jbc.m115.644724 CrossRefPubMedPubMedCentralGoogle Scholar
  113. Ward RJ, Pediani JD, Harikumar KG, Miller LJ, Milligan G (2017) Spatial intensity distribution analysis quantifies the extent and regulation of homodimerization of the secretin receptor. Biochem J 474:1879–1895.  https://doi.org/10.1042/bcj20170184 CrossRefPubMedPubMedCentralGoogle Scholar
  114. Wensel TG, Zhang Z, Anastassov IA, Gilliam JC, He F, Schmid MF, Robichaux MA (2016) Structural and molecular bases of rod photoreceptor morphogenesis and disease. Prog Retin Eye Res 55:32–51.  https://doi.org/10.1016/j.preteyeres.2016.06.002 CrossRefPubMedPubMedCentralGoogle Scholar
  115. Whited AM, Park PS (2014) Atomic force microscopy: a multifaceted tool to study membrane proteins and their interactions with ligands. Biochim Biophys Acta 1838:56–68.  https://doi.org/10.1016/j.bbamem.2013.04.011 CrossRefPubMedGoogle Scholar
  116. Whited AM, Park PSH (2015) Nanodomain organization of rhodopsin in native human and murine rod outer segment disc membranes. Bba-Biomembranes 1848:26–34.  https://doi.org/10.1016/j.bbamem.2014.10.007 CrossRefPubMedGoogle Scholar
  117. Wiedmann TS, Pates RD, Beach JM, Salmon A, Brown MF (1988) Lipid-protein interactions mediate the photochemical function of rhodopsin. Biochemistry 27:6469–6474CrossRefGoogle Scholar
  118. Williams TP, Penn JS (1985) Intracellular topography of rhodopsin regeneration in vertebrate rods. J Gen Physiol 86:413–422CrossRefGoogle Scholar
  119. Young JE, Albert AD (2000) Transducin binding in bovine rod outer segment disk membranes of different age/spatial location. Exp Eye Res 70:809–812.  https://doi.org/10.1006/exer.2000.0821 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Ophthalmology and Visual SciencesCase Western Reserve UniversityClevelandUSA

Personalised recommendations