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Light-Dependent Compartmentalization of Transducin in Rod Photoreceptors

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Abstract

Three major visual signaling proteins, transducin, arrestin, and recoverin undergo bidirectional translocations between the outer segment and inner compartments of rod photoreceptors in a light-dependent manner. The light-dependent translocation of proteins is believed to contribute to adaptation and neuroprotection of photoreceptor cells. The potential physiological significance and mechanisms of light-controlled protein translocations are at the center of current discussion. In this paper, I outline the latest advances in understanding the mechanisms of bidirectional translocation of transducin and determinants of its steady-state distribution in dark- and light-adapted photoreceptor cells.

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References

  1. Burns ME, Arshavsky VY (2005) Beyond counting photons: trials and trends in vertebrate visual transduction. Neuron 48:387–401

    Article  PubMed  CAS  Google Scholar 

  2. Lamb TD, Pugh EN Jr (2006) Phototransduction, dark adaptation, and rhodopsin regeneration the proctor lecture. Invest Ophthalmol Vis Sci 47:5137–5152

    Article  PubMed  Google Scholar 

  3. Fu Y, Yau KW (2007) Phototransduction in mouse rods and cones. Pflugers Arch 454:805–819

    Article  PubMed  CAS  Google Scholar 

  4. Strauss O (2005) The retinal pigment epithelium in visual function. Physiol Rev 85:845–881

    Article  PubMed  CAS  Google Scholar 

  5. Brann MR, Cohen LV (1987) Diurnal expression of transducin mRNA and translocation of transducin in rods of rat retina. Science 235:585–587

    Article  PubMed  CAS  Google Scholar 

  6. Philp NJ, Chang W, Long K (1987) Light-stimulated protein movement in rod photoreceptor cells of the rat retina. FEBS Lett 225:127–132

    Article  PubMed  CAS  Google Scholar 

  7. Whelan JP, McGinnis JF (1988) Light-dependent subcellular movement of photoreceptor proteins. J Neurosci Res 20:263–270

    Article  PubMed  CAS  Google Scholar 

  8. Sokolov M, Lyubarsky AL, Strissel KJ, Savchenko AB, Govardovskii VI, Pugh EN Jr, Arshavsky VY (2002) Massive light-driven translocation of transducin between the two major compartments of rod cells: a novel mechanism of light adaptation. Neuron 34:95–106

    Article  PubMed  CAS  Google Scholar 

  9. Nair KS, Hanson SM, Mendez A, Gurevich EV, Kennedy MJ, Shestopalov VI, Vishnivetskiy SA, Chen J, Hurley JB, Gurevich VV, Slepak VZ (2005) Light-dependent redistribution of arrestin in vertebrate rods is an energy-independent process governed by protein-protein interactions. Neuron 46:555–567

    Article  PubMed  CAS  Google Scholar 

  10. Strissel KJ, Lishko PV, Trieu LH, Kennedy MJ, Hurley JB, Arshavsky VY (2005) Recoverin undergoes light-dependent intracellular translocation in rod photoreceptors. J Biol Chem 280:29250–29255

    Article  PubMed  CAS  Google Scholar 

  11. Fain GL (2006) Why photoreceptors die (and why they don’t). Bioessays 28:344–354

    Article  PubMed  CAS  Google Scholar 

  12. Calvert PD, Strissel KJ, Schiesser WE, Pugh EN Jr, Arshavsky VY (2006) Light-driven translocation of signaling proteins in vertebrate photoreceptors. Trends Cell Biol 16:560–568

    Article  PubMed  CAS  Google Scholar 

  13. Calvert PD, Strissel KJ, Schiesser WE, Pugh EN, Arshavsky VY (2006) Arrestin translocation is induced at a critical threshold of visual signaling and is superstoichiometric to bleached rhodopsin. J Neurosci 26:1146–1153

    Article  CAS  Google Scholar 

  14. Lobanova ES, Finkelstein S, Song H, Tsang SH, Chen CK, Sokolov M, Skiba NP, Arshavsky VY (2007) Transducin translocation in rods is triggered by saturation of the GTPase-activating complex. J Neurosci 27:1151–1160

    Article  PubMed  CAS  Google Scholar 

  15. Rosenzweig DH, Nair KS, Wei J, Wang Q, Garwin G, Saari JC, Chen CK, Smrcka AV, Swaroop A, Lem J, Hurley JB, Slepak VZ (2007) Subunit dissociation and diffusion determine the subcellular localization of rod and cone transducins. J Neurosci 27:5484–5494

    Article  PubMed  CAS  Google Scholar 

  16. Kerov V, Rubin WW, Natochin M, Melling N, Burns ME, Artemyev NO (2007) N-terminal fatty acylation of transducin profoundly influences its localization and the kinetics of photoresponse in rods. J Neurosci 27:10270–10277

    Article  PubMed  CAS  Google Scholar 

  17. Wedegaertner PB, Wilson PT, Bourne HR (1995) Lipid modifications of trimeric G proteins. J Biol Chem 270:503–506

    Article  PubMed  CAS  Google Scholar 

  18. Chen CA, Manning DR (2001) Regulation of G proteins by covalent modification. Oncogene 20:1643–1652

    Article  PubMed  CAS  Google Scholar 

  19. Karan S, Zhang H, Li S, Frederick JM, Baehr W (2008) A model for transport of membrane-associated phototransduction polypeptides in rod and cone photoreceptor inner segments. Vis Res 48:442–452

    Article  PubMed  CAS  Google Scholar 

  20. Neubert TA, Johnson RS, Hurley JB, Walsh KA (1992) The rod transducin a subunit amino terminus is heterogeneously fatty acylated. J Biol Chem 267:18274–18277

    PubMed  CAS  Google Scholar 

  21. Bhatnagar RS, Schall OF, Jackson-Machelski E, Sikorski JA, Devadas B, Gokel GW, Gordon JI (1997) Titration calorimetric analysis of AcylCoA recognition by myristoylCoA:protein N-myristoyltransferase. Biochemistry 36:6700–6708

    Article  PubMed  CAS  Google Scholar 

  22. Bigay J, Faurobert E, Franco M, Chabre M (1994) Roles of lipid modifications of transducin subunits in their GDP-dependent association and membrane binding. Biochemistry 33:14081–14090

    Article  PubMed  CAS  Google Scholar 

  23. Resh MD (1999) Fatty acylation of proteins: new insights into membrane targeting of myristoylated and palmitoylated proteins. Biochim Biophys Acta 1451:1–16

    Article  PubMed  CAS  Google Scholar 

  24. Kosloff M, Elia N, Selinger Z (2002) Structural homology discloses a bifunctional structural motif at the N-termini of Ga proteins. Biochemistry 41:14518–14523

    Article  PubMed  CAS  Google Scholar 

  25. Lai RK, Perez-Sala D, Cañada FJ, Rando RR (1990) The g subunit of transducin is farnesylated. Proc Natl Acad Sci U S A 87:7673–7677

    Article  PubMed  CAS  Google Scholar 

  26. Fukada Y, Takao T, Ohguro H, Yoshizawa T, Akino T, Shimonishi Y (1990) Farnesylated g-subunit of photoreceptor G protein indispensable for GTP-binding. Nature 346:658–660

    Article  PubMed  CAS  Google Scholar 

  27. Higgins JB, Casey PJ (1996) The role of prenylation in G-protein assembly and function. Cell Signal 8:433–437

    Article  PubMed  CAS  Google Scholar 

  28. Marrari Y, Crouthamel M, Irannejad R, Wedegaertner PB (2007) Assembly and trafficking of heterotrimeric G proteins. Biochemistry 46:7665–767

    Article  PubMed  CAS  Google Scholar 

  29. Fu HW, Casey PJ (1999) Enzymology and biology of CaaX protein prenylation. Recent Prog Horm Res 54:315–342

    PubMed  CAS  Google Scholar 

  30. Gelb MH, Brunsveld L, Hrycyna CA, Michaelis S, Tamanoi F, Voorhis WCV, Waldmann H (2006) Therapeutic intervention based on protein prenylation and associated modifications. Nat Chem Biol 2:518–528

    Article  PubMed  CAS  Google Scholar 

  31. Michaelson D, Ahearn I, Bergo M, Young S, Philips M (2002) Membrane trafficking of heterotrimeric G proteins via the endoplasmic reticulum and Golgi. Mol Biol Cell 13:3294–3302

    Article  PubMed  CAS  Google Scholar 

  32. Takida S, Wedegaertner PB (2003) Heterotrimer formation, together with isoprenylation, is required for plasma membrane targeting of Gbg. J Biol Chem 278:17284–17290

    Article  PubMed  CAS  Google Scholar 

  33. Zhang H, Huang W, Zhang H, Zhu X, Craft CM, Baehr W, Chen C-K (2003) Light-dependent redistribution of visual arrestins and transducin subunits in mice with defective phototransduction. Mol Vis 9:231–237

    PubMed  CAS  Google Scholar 

  34. Kerov V, Chen D, Moussaif M, Chen YJ, Chen CK, Artemyev NO (2005) Transducin activation state controls its light-dependent translocation in rod photoreceptors. J Biol Chem 280:41069–41076

    Article  PubMed  CAS  Google Scholar 

  35. Natochin M, Barren B, Artemyev NO (2006) Dominant negative mutants of transducin-a that block activated receptor. Biochemistry 45:6488–6494

    Article  PubMed  CAS  Google Scholar 

  36. Peterson JJ, Orisme W, Fellows J, McDowell JH, Shelamer CL, Dugger DR, Smith WC (2005) A role for cytoskeletal elements in the light-driven translocation of proteins in rod photoreceptors. Invest Ophthalmol Vis Sci 46:3988–3998

    Article  PubMed  Google Scholar 

  37. Reidel B, Giebl A, Wolfrum U (2006) Arrestin and transducin translocations associated with the dark adaptation of rod photoreceptor cells are fully dependent on the cytoskeleton [abstract]. Invest Ophthalmol Vis Sci 47:ARVO E-Abstract 5528

  38. Willardson BM, Howlett AC (2007) Function of phosducin-like proteins in G protein signaling and chaperone-assisted protein folding. Cell Signal 19:2417–2427

    Article  PubMed  CAS  Google Scholar 

  39. Gaudet R, Bohm A, Sigler PB (1996) Crystal structure at 2.4 angstroms resolution of the complex of transducin bg and its regulator, phosducin. Cell 87:577–588

    Article  PubMed  CAS  Google Scholar 

  40. Loew A, Ho YK, Blundell T, Bax B (1998) Phosducin induces a structural change in transducin bg. Structure 6:1007–1019

    Article  PubMed  CAS  Google Scholar 

  41. Sokolov M, Strissel KJ, Leskov IB, Michaud NA, Govardovskii VI, Arshavsky VY (2004) Phosducin facilitates light-driven transducin translocation in rod photoreceptors. Evidence from the phosducin knockout mouse. J Biol Chem 279:19149–19156

    Article  PubMed  CAS  Google Scholar 

  42. Krispel CM, Sokolov M, Chen Y, Song H, Herrmann R, Arshavsky VY, Burns ME (2007) Phosducin regulates the expression of transducin bg subunits in rod photoreceptors and does not contribute to phototransduction adaptation. J Gen Physiol 130:303–312

    Article  PubMed  CAS  Google Scholar 

  43. Obin M, Lee BY, Meinke G, Bohm A, Lee RH, Gaudet R, Hopp JA, Arshavsky VY, Willardson BM, Taylor A (2002) Ubiquitylation of the transducin bg subunit complex. Regulation by phosducin. J Biol Chem 277:44566–44575

    Article  PubMed  CAS  Google Scholar 

  44. Song H, Belcastro M, Young EJ, Sokolov M (2007) Compartment-specific phosphorylation of phosducin in rods underlies adaptation to various levels of illumination. J Biol Chem 282:23613–23621

    Article  PubMed  CAS  Google Scholar 

  45. Gillespie PG, Prusti RK, Apel ED, Beavo JA (1989) A soluble form of bovine rod photoreceptor phosphodiesterase has a novel 15-kDa subunit. J Biol Chem 264:12187–12193

    PubMed  CAS  Google Scholar 

  46. Florio SK, Prusti RK, Beavo JA (1996) Solubilization of membrane-bound rod phosphodiesterase by the rod phosphodiesterase recombinant delta subunit. J Biol Chem 271:24036–24047

    Article  PubMed  CAS  Google Scholar 

  47. Norton AW, Hosier S, Terew JM, Li N, Dhingra A, Vardi N, Baehr W, Cote RH (2005) Evaluation of the 17-kDa prenyl-binding protein as a regulatory protein for phototransduction in retinal photoreceptors. J Biol Chem 280:1248–1256

    Article  PubMed  CAS  Google Scholar 

  48. Zhang H, Li S, Doan T, Rieke F, Detwiler PB, Frederick JM, Baehr W (2007) Deletion of PrBP/d impedes transport of GRK1 and PDE6 catalytic subunits to photoreceptor outer segments. Proc Natl Acad Sci USA 104:8857–8862

    Article  PubMed  CAS  Google Scholar 

  49. Matsuoka K, Orci L, Amherdt M, Bednarek SY, Hamamoto S, Schekman R, Yeung T (1998) COPII-coated vesicle formation reconstituted with purified coat proteins and chemically defined liposomes. Cell 93:263–275

    Article  PubMed  CAS  Google Scholar 

  50. Chen J, Wu M, Sezate SA, Matsumoto H, Ramsey M, McGinnis JF (2008) Interaction of glyceraldehyde-3-phosphate dehydrogenase in the light-induced rod a-transducin translocation. J Neurochem 104:1280–1292

    Article  PubMed  CAS  Google Scholar 

  51. Hsu SC, Molday RS (1990) Glyceraldehyde-3-phosphate dehydrogenase is a major protein associated with the plasma membrane of retinal photoreceptor outer segments. J Biol Chem 265:13308–13313

    PubMed  CAS  Google Scholar 

  52. Roepman R, Wolfrum U (2007) Protein networks and complexes in photoreceptor cilia. Subcell Biochem 43:209–235

    Article  PubMed  Google Scholar 

  53. Giessl A, Trojan P, Rausch S, Pulvermüller A, Wolfrum U (2006) Centrins, gatekeepers for the light-dependent translocation of transducin through the photoreceptor cell connecting cilium. Vis Res 46:4502–4509

    Article  PubMed  CAS  Google Scholar 

  54. Scholey JM (2003) Intraflagellar transport. Annu Rev Cell Dev Biol 19:423–443

    Article  PubMed  CAS  Google Scholar 

  55. Pazour GJ, Baker SA, Deane JA, Cole DG, Dickert BL, Rosenbaum JL, Witman GB, Besharse JC (2002) The intraflagellar transport protein, IFT88, is essential for vertebrate photoreceptor assembly and maintenance. J Cell Biol 157:103–113

    Article  PubMed  CAS  Google Scholar 

  56. Luby-Phelps K, Fogerty J, Baker SA, Pazour GJ, Besharse JC (2008) Spatial distribution of intraflagellar transport proteins in vertebrate photoreceptors. Vis Res 48:413–423

    Article  PubMed  CAS  Google Scholar 

  57. Marszalek JR, Liu X, Roberts EA, Chui D, Marth JD, Williams DS, Goldstein LS (2000) Genetic evidence for selective transport of opsin and arrestin by kinesin-II in mammalian photoreceptors. Cell 102:175–187

    Article  PubMed  CAS  Google Scholar 

  58. Baehr W, Karan S, Maeda T, Luo D, Li S, Bronson JD, Watt CB, Yau K, Frederick JM, Palczewski K (2007) The function of guanylate cyclase 1 and guanylate cyclase 2 in rod and cone photoreceptors. J Biol Chem 282:8837–8847

    Article  PubMed  CAS  Google Scholar 

  59. Alves ID, Salgado GFJ, Salamon Z, Brown MF, Tollin G, Hruby VJ (2005) Phosphatidylethanolamine enhances rhodopsin photoactivation and transducin binding in a solid supported lipid bilayer as determined using plasmon-waveguide resonance spectroscopy. Biophys J 88:198–210

    Article  PubMed  CAS  Google Scholar 

  60. Fanelli F, Dell'Orco D (2005) Rhodopsin activation follows precoupling with transducin: inferences from computational analysis. Biochemistry 44:14695–14700

    Article  PubMed  CAS  Google Scholar 

  61. Kerov VS, Natochin M, Artemyev NO (2005) Interaction of transducin-a with LGN, a G-protein modulator expressed in photoreceptor cells. Mol Cell Neurosci 28:485–495

    Article  PubMed  CAS  Google Scholar 

  62. Nair KS, Mendez A, Blumer JB, Rosenzweig DH, Slepak VZ (2005) The presence of a Leu-Gly-Asn repeat-enriched protein (LGN), a putative binding partner of transducin, in ROD photoreceptors. Invest Ophthalmol Vis Sci 46:383–389

    Article  PubMed  Google Scholar 

  63. Kassai H, Aiba A, Nakao K, Nakamura K, Katsuki M, Xiong WH, Yau KW, Imai H, Shichida Y, Satomi Y, Takao T, Okano T, Fukada Y (2005) Farnesylation of retinal transducin underlies its translocation during light adaptation. Neuron 47:529–539

    Article  PubMed  CAS  Google Scholar 

  64. Mendez A, Lem J, Simon M, Chen J (2003) Light-dependent translocation of arrestin in the absence of rhodopsin phosphorylation and transducin signaling. J Neurosci 23:3124–3129

    PubMed  CAS  Google Scholar 

  65. Catty P, Pfister C, Bruckert F, Deterre P (1992) The cGMP phosphodiesterase-transducin complex of retinal rods. Membrane binding and subunits interactions. J Biol Chem 267:19489–19493

    PubMed  CAS  Google Scholar 

  66. Clerc A, Bennett N (1992) Activated cGMP phosphodiesterase of retinal rods. A complex with transducin a subunit. J Biol Chem 267:6620–6627

    PubMed  CAS  Google Scholar 

  67. Tsang SH, Burns ME, Calvert PD, Gouras P, Baylor DA, Goff SP, Arshavsky VY (1998) Role for the target enzyme in deactivation of photoreceptor G protein in vivo. Science 282:117–121

    Article  PubMed  CAS  Google Scholar 

  68. Kennedy MJ, Dunn FA, Hurley JB (2004) Visual pigment phosphorylation but not transducin translocation can contribute to light adaptation in zebrafish cones. Neuron 41:915–928

    Article  PubMed  CAS  Google Scholar 

  69. Elias RV, Sezate SS, Cao W, McGinnis JF (2004) Temporal kinetics of the light/dark translocation and compartmentation of arrestin and a-transducin in mouse photoreceptor cells. Mol Vis 10:672–681

    PubMed  CAS  Google Scholar 

  70. Coleman JE, Semple-Rowland SL (2005) GC1 deletion prevents light-dependent arrestin translocation in mouse cone photoreceptor cells. Invest Ophthalmol Vis Sci 46:12–16

    Article  PubMed  Google Scholar 

  71. Chen J, Wu M, Sezate SA, McGinnis JF (2007) Light threshold-controlled cone a-transducin translocation. Invest Ophthalmol Vis Sci 48:3350–3355

    Article  PubMed  Google Scholar 

  72. McGinnis JF, Matsumoto B, Whelan JP, Cao W (2002) Cytoskeleton participation in subcellular trafficking of signal transduction proteins in rod photoreceptor cells. J Neurosci Res 67:290–297

    Article  PubMed  CAS  Google Scholar 

  73. Peet JA, Bragin A, Calvert PD, Nikonov SS, Mani S, Zhao X, Besharse JC, Pierce EA, Knox BE, Pugh EN Jr (2004) Quantification of the cytoplasmic spaces of living cells with EGFP reveals arrestin-EGFP to be in disequilibrium in dark adapted rod photoreceptors. J Cell Sci 117:3049–3059

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

I thank Drs. Vadim Arshavsky and Mark Stamnes for critically reading the manuscript and valuable comments and Vasily Kerov for creating illustrations. The author’s work is supported by National Institutes of Health Grant RO1 EY-12682.

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  1. Department of Molecular Physiology and Biophysics, University of Iowa College of Medicine, 5-532 Bowen Science Building, 51 Newton Road, Iowa, IA, 52242, USA

    Nikolai O. Artemyev

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Artemyev, N.O. Light-Dependent Compartmentalization of Transducin in Rod Photoreceptors. Mol Neurobiol 37, 44–51 (2008). https://doi.org/10.1007/s12035-008-8015-2

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