Selective impairment of a subset of Ran-GTP-binding domains of Ran-binding protein 2 (Ranbp2) suffices to recapitulate the degeneration of the retinal pigment epithelium (RPE) triggered by Ranbp2 ablation

Journal of Biological Chemistry

Volumn 289, Issue 43, 2014, Pages 29767-29789

  Patil, Hemangi ^a   Saha, Arjun ^a   Senda, Eugene ^a   Cho, Kyoung In ^a   Haque, MdEmdadul ^a,e   Yu, Minzhong ^b   Qiu, Sunny ^a   Yoon, Dosuk ^a   Hao, Ying ^a   Peachey, Neal S ^b,c,d   Ferreira, Paulo A ^a  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

^b LERNER RESEARCH INSTITUTE   (United States)

^c LOUIS STOKES CLEVELAND VA MEDICAL CENTER   (United States)

^d CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE   (United States)

^e SYNGENTA BIOTECHNOLOGY INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ABLATION; ALDEHYDES; DEREGULATION; DISEASE CONTROL; ELECTROPHYSIOLOGY; ENZYME ACTIVITY; OPHTHALMOLOGY; TISSUE HOMEOSTASIS;

BACTERIAL ARTIFICIAL CHROMOSOMES; CELLULAR VIABILITY; CONE PHOTORECEPTORS; ELECTROPHYSIOLOGICAL RESPONSE; GENETIC COMPLEMENTATION; RETINAL PIGMENT EPITHELIUM; SUBCELLULAR LOCALIZATIONS; THERAPEUTIC TARGETS;

PROTEINS;

F ACTIN; GAMMA TUBULIN; RAN BINDING PROTEIN 2; RAN PROTEIN; SEROTRANSFERRIN; STROMELYSIN 3; TRANSFERRIN; UNCLASSIFIED DRUG; CHAPERONE; CRE RECOMBINASE; INTEGRASE; NUCLEOPORIN; RAN-BINDING PROTEIN 2;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; APOPTOSIS; ARTICLE; ATROPHY; BACTERIAL ARTIFICIAL CHROMOSOME; BLOOD RETINA BARRIER; CELL PROLIFERATION; CHOROID CAPILLARY LAYER; ELECTROPHYSIOLOGY; ENZYME ACTIVATION; GENETIC COMPLEMENTATION; HYPOPLASIA; KNOCKOUT MOUSE; LIGHT EVOKED ELECTROPHYSIOLOGICAL RESPONSE; LOSS OF FUNCTION MUTATION; MOUSE; NONHUMAN; PROTEIN BINDING; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN HOMEOSTASIS; PROTEIN LOCALIZATION; RANBP2 GENE; RETINA CONE; RETINA PIGMENT DEGENERATION; STIMULUS RESPONSE; SYNCYTIUM; TRANSGENIC MOUSE; VISUAL SYSTEM PARAMETERS; ANIMAL; CAPILLARY; CELL SURVIVAL; CHEMISTRY; DEFICIENCY; DISEASE COURSE; GENE DELETION; GENETICS; METABOLISM; MUTATION; PATHOLOGY; PATHOPHYSIOLOGY; PIGMENT EPITHELIUM; PROTEIN TERTIARY STRUCTURE; STRUCTURE ACTIVITY RELATION; ULTRASTRUCTURE;

ANIMALS; CAPILLARIES; CELL PROLIFERATION; CELL SURVIVAL; CHROMOSOMES, ARTIFICIAL, BACTERIAL; DISEASE PROGRESSION; ELECTROPHYSIOLOGICAL PHENOMENA; GENE DELETION; INTEGRASES; MICE; MICE, TRANSGENIC; MOLECULAR CHAPERONES; MUTATION; NUCLEAR PORE COMPLEX PROTEINS; PROTEIN STRUCTURE, TERTIARY; RETINAL PIGMENT EPITHELIUM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84908178816     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M114.586834     Document Type: Article

References (96)

1. Bok, D. (1993) The retinal pigment epithelium: a versatile partner in vision. J. Cell Sci. Suppl. 17, 189-195
2. Strauss, O. (2005) The retinal pigment epithelium in visual function. Physiol. Rev. 85, 845-881
3. Marmor, M. F., and Wolfensberger, T. J. (1998) The Retinal Pigment Epithelium: Current Aspects of Function and Disease, Oxford University Press, New York
4. Rattner, A., and Nathans, J. (2006) Macular degeneration: recent advances and therapeutic opportunities. Nat. Rev. Neurosci. 7, 860-872
5. Jager, R. D., Mieler, W. F., and Miller, J. W. (2008) Age-related macular degeneration. N. Engl. J. Med. 358, 2606-2617
6. Bird, A. C., Bressler, N. M., Bressler, S. B., Chisholm, I. H., Coscas, G., Davis, M. D., de Jong, P. T., Klaver, C. C., Klein, B. E., and Klein, R. (1995) An international classification and grading system for age-related maculopathy and age-related macular degeneration. The International ARM Epidemiological Study Group. Surv. Ophthalmol. 39, 367-374
7. Marmorstein, A. D., Cross, H. E., and Peachey, N. S. (2009) Functional roles of bestrophins in ocular epithelia. Prog. Retin. Eye Res. 28, 206-226
8. Maw, M. A., Kennedy, B., Knight, A., Bridges, R., Roth, K. E., Mani, E. J., Mukkadan, J. K., Nancarrow, D., Crabb, J. W., and Denton, M. J. (1997) Mutation of the gene encoding cellular retinaldehyde-binding protein in autosomal recessive retinitis pigmentosa. Nat. Genet. 17, 198-200
9. Marlhens, F., Bareil, C., Griffoin, J. M., Zrenner, E., Amalric, P., Eliaou, C., Liu, S. Y., Harris, E., Redmond, T. M., Arnaud, B., Claustres, M., and Hamel, C. P. (1997) Mutations in RPE65 cause Leber's congenital amaurosis. Nat. Genet. 17, 139-141
10. Marmorstein, L. Y., Munier, F. L., Arsenijevic, Y., Schorderet, D. F., McLaughlin, P. J., Chung, D., Traboulsi, E., and Marmorstein, A. D. (2002) Aberrant accumulation of EFEMP1 underlies drusen formation in malattia leventinese and age-related macular degeneration. Proc. Natl. Acad. Sci. U.S.A. 99, 13067-13072
11. Stone, E. M., Lotery, A. J., Munier, F. L., Héon, E., Piguet, B., Guymer, R. H., Vandenburgh, K., Cousin, P., Nishimura, D., Swiderski, R. E., Silvestri, G., Mackey, D. A., Hageman, G. S., Bird, A. C., Sheffield, V. C., and Schorderet, D. F. (1999) A single EFEMP1 mutation associated with both malattia leventinese and Doyne honeycomb retinal dystrophy. Nat. Genet. 22, 199-202
12. Weber, B. H., Vogt, G., Pruett, R. C., Stöhr, H., and Felbor, U. (1994) Mutations in the tissue inhibitor of metalloproteinases-3 (TIMP3) in patients with Sorsby's fundus dystrophy. Nat. Genet. 8, 352-356
13. Suzuki, M., Tsujikawa, M., Itabe, H., Du, Z. J., Xie, P., Matsumura, N., Fu, X., Zhang, R., Sonoda, K. H., Egashira, K., Hazen, S. L., and Kamei, M. (2012) Chronic photo-oxidative stress and subsequent MCP-1 activation as causative factors for age-related macular degeneration. J. Cell Sci. 125, 2407-2415
14. Yates, J. R., Sepp, T., Matharu, B. K., Khan, J. C., Thurlby, D. A., Shahid, H., Clayton, D. G., Hayward, C., Morgan, J., Wright, A. F., Armbrecht, A. M., Dhillon, B., Deary, I. J., Redmond, E., Bird, A. C., and Moore, A. T. (2007) Complement C3 variant and the risk of age-related macular degeneration. N. Engl. J. Med. 357, 553-561
15. Taylor, H. R., West, S., Muñoz, B., Rosenthal, F. S., Bressler, S. B., and Bressler, N. M. (1992) The long-term effects of visible light on the eye. Arch. Ophthalmol. 110, 99-104
16. Cruickshanks, K. J., Klein, R., and Klein, B. E. (1993) Sunlight and age-related macular degeneration. The Beaver Dam Eye Study. Arch. Ophthalmol. 111, 514-518
17. Edwards, A. O., Ritter, R., 3rd, Abel, K. J., Manning, A., Panhuysen, C., and Farrer, L. A. (2005) Complement factor H polymorphism and age-related macular degeneration. Science 308, 421-424
18. Hollyfield, J. G., Bonilha, V. L., Rayborn, M. E., Yang, X., Shadrach, K. G., Lu, L., Ufret, R. L., Salomon, R. G., and Perez, V. L. (2008) Oxidative damage-induced inflammation initiates age-related macular degeneration. Nat. Med. 14, 194-198
19. Weismann, D., Hartvigsen, K., Lauer, N., Bennett, K. L., Scholl, H. P., Charbel Issa, P., Cano, M., Brandstätter, H., Tsimikas, S., Skerka, C., Superti-Furga, G., Handa, J. T., Zipfel, P. F., Witztum, J. L., and Binder, C. J. (2011) Complement factor H binds malondialdehyde epitopes and protects from oxidative stress. Nature 478, 76-81
20. Imamura, Y., Noda, S., Hashizume, K., Shinoda, K., Yamaguchi, M., Uchiyama, S., Shimizu, T., Mizushima, Y., Shirasawa, T., and Tsubota, K. (2006) Drusen, choroidal neovascularization, and retinal pigment epithelium dysfunction in SOD1-deficient mice: a model of age-related macular degeneration. Proc. Natl. Acad. Sci. U.S.A. 103, 11282-11287
21. Boulton, M., and Dayhaw-Barker, P. (2001) The role of the retinal pigment epithelium: topographical variation and ageing changes. Eye 15, 384-389
22. Cho, K. I., Yi, H., Tserentsoodol, N., Searle, K., and Ferreira, P. A. (2010) Neuroprotection resulting from insufficiency of RANBP2 is associated with the modulation of protein and lipid homeostasis of functionally diverse but linked pathways in response to oxidative stress. Dis. Model. Mech. 3, 595-604
23. Cho, K. I., Yi, H., Yeh, A., Tserentsoodol, N., Cuadrado, L., Searle, K., Hao, Y., and Ferreira, P. A. (2009) Haploinsufficiency of RanBP2 is neuroprotective against light-elicited and age-dependent degeneration of photoreceptor neurons. Cell Death Differ. 16, 287-297
24. Aslanukov, A., Bhowmick, R., Guruju, M., Oswald, J., Raz, D., Bush, R. A., Sieving, P. A., Lu, X., Bock, C. B., and Ferreira, P. A. (2006) RanBP2 modulates Cox11 and hexokinase I activities and haploinsufficiency of RanBP2 causes deficits in glucose metabolism. PLoS Genet. 2, e177
25. Cho, K. I., Searle, K., Webb, M., Yi, H., and Ferreira, P. A. (2012) Ranbp2 haploinsufficiency mediates distinct cellular and biochemical phenotypes in brain and retinal dopaminergic and glia cells elicited by the Parkinsonian neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Cell. Mol. Life Sci. 69, 3511-3527
26. Dawlaty, M. M., Malureanu, L., Jeganathan, K. B., Kao, E., Sustmann, C., Tahk, S., Shuai, K., Grosschedl, R., and van Deursen, J. M. (2008) Resolution of sister centromeres requires RanBP2-mediated SUMOylation of topoisomerase IIα. Cell 133, 103-115
27. Um, J. W., Min, D. S., Rhim, H., Kim, J., Paik, S. R., and Chung, K. C. (2006) Parkin ubiquitinates and promotes the degradation of RanBP2. J. Biol. Chem. 281, 3595-3603
28. Um, J. W., and Chung, K. C. (2006) Functional modulation of parkin through physical interaction with SUMO-1. J. Neurosci. Res. 84, 1543-1554
29. Shimura, H., Hattori, N., Kubo, S., Mizuno, Y., Asakawa, S., Minoshima, S., Shimizu, N., Iwai, K., Chiba, T., Tanaka, K., and Suzuki, T. (2000) Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat. Genet. 25, 302-305
30. Dawson, T. M., and Dawson, V. L. (2010) The role of parkin in familial and sporadic Parkinson's disease. Mov. Disord. 25, S32-S39
31. Dawson, T. M., and Dawson, V. L. (2014) Parkin plays a role in sporadic Parkinson's disease. Neurodegener. Dis. 13, 69-71
32. Veeriah, S., Taylor, B. S., Meng, S., Fang, F., Yilmaz, E., Vivanco, I., Janakiraman, M., Schultz, N., Hanrahan, A. J., Pao, W., Ladanyi, M., Sander, C., Heguy, A., Holland, E. C., Paty, P. B., Mischel, P. S., Liau, L., Cloughesy, T. F., Mellinghoff, I. K., Solit, D. B., and Chan, T. A. (2010) Somatic mutations of the Parkinson's disease-associated gene PARK2 in glioblastoma and other human malignancies. Nat. Genet. 42, 77-82
33. Poulogiannis, G., McIntyre, R. E., Dimitriadi, M., Apps, J. R., Wilson, C. H., Ichimura, K., Luo, F., Cantley, L. C., Wyllie, A. H., Adams, D. J., and Arends, M. J. (2010) PARK2 deletions occur frequently in sporadic colorectal cancer and accelerate adenoma development in Apc mutant mice. Proc. Natl. Acad. Sci. U.S.A. 107, 15145-15150
34. Cho, K. I., Haque, M., Wang, J., Yu, M., Hao, Y., Qiu, S., Pillai, I. C., Peachey, N. S., and Ferreira, P. A. (2013) Distinct and atypical intrinsic and extrinsic cell death pathways between photoreceptor cell types upon specific ablation of Ranbp2 in cone photoreceptors. PLoS Genet. 9, e1003555
35. Neilson, D. E., Adams, M. D., Orr, C. M., Schelling, D. K., Eiben, R. M., Kerr, D. S., Anderson, J., Bassuk, A. G., Bye, A. M., Childs, A. M., Clarke, A., Crow, Y. J., Di Rocco, M., Dohna-Schwake, C., Dueckers, G., Fasano, A. E., Gika, A. D., Gionnis, D., Gorman, M. P., Grattan-Smith, P. J., Hackenberg, A., Kuster, A., Lentschig, M. G., Lopez-Laso, E., Marco, E. J., Mastroyianni, S., Perrier, J., Schmitt-Mechelke, T., Servidei, S., Skardoutsou, A., Uldall, P., van der Knaap, M. S., Goglin, K. C., Tefft, D. L., Aubin, C., de Jager, P., Hafler, D., and Warman, M. L. (2009) Infection-triggered familial or recurrent cases of acute necrotizing encephalopathy caused by mutations in a component of the nuclear pore, RANBP2. Am. J. Hum. Genet. 84, 44-51
36. Wolf, K., Schmitt-Mechelke, T., Kollias, S., and Curt, A. (2013) Acute necrotizing encephalopathy (ANE1): rare autosomal-dominant disorder presenting as acute transverse myelitis. J. Neurol. 260, 1545-1553
37. Lönnqvist, T., Isohanni, P., Valanne, L., Olli-Lähdesmäki, T., Suomalainen, A., and Pihko, H. (2011) Dominant encephalopathy mimicking mitochondrial disease. Neurology 76, 101-103
38. Ferreira, P. A., Hom, J. T., and Pak, W. L. (1995) Retina-specifically expressed novel subtypes of bovine cyclophilin. J. Biol. Chem. 270, 23179-23188
39. Wu, J., Matunis, M. J., Kraemer, D., Blobel, G., and Coutavas, E. (1995) Nup358, a cytoplasmically exposed nucleoporin with peptide repeats, Ran-GTP binding sites, zinc fingers, a cyclophilin A homologous domain, and a leucine-rich region. J. Biol. Chem. 270, 14209-14213
40. Yokoyama, N., Hayashi, N., Seki, T., Panté, N., Ohba, T., Nishii, K., Kuma, K., Hayashida, T., Miyata, T., and Aebi, U. (1995) A giant nucleopore protein that binds Ran/TC4. Nature 376, 184-188
41. Künzler, M., Trueheart, J., Sette, C., Hurt, E., and Thorner, J. (2001) Mutations in the YRB1 gene encoding yeast ran-binding-protein-1 that impair nucleocytoplasmic transport and suppress yeast mating defects. Genetics 157, 1089-1105
42. Coutavas, E., Ren, M., Oppenheim, J. D., D'Eustachio, P., and Rush, M. G. (1993) Characterization of proteins that interact with the cell-cycle regulatory protein Ran/TC4. Nature 366, 585-587
43. Villa Braslavsky, C. I., Nowak, C., Görlich, D., Wittinghofer, A., and Kuhlmann, J. (2000) Different structural and kinetic requirements for the interaction of Ran with the Ran-binding domains from RanBP2 and importin-β. Biochemistry 39, 11629-11639
44. Ciccarelli, F. D., von Mering, C., Suyama, M., Harrington, E. D., Izaurralde, E., and Bork, P. (2005) Complex genomic rearrangements lead to novel primate gene function. Genome Res. 15, 343-351
45. Riddick, G., and Macara, I. G. (2005) A systems analysis of importin-α-β mediated nuclear protein import. J. Cell Biol. 168, 1027-1038
46. Smith, A. E., Slepchenko, B. M., Schaff, J. C., Loew, L. M., and Macara, I. G. (2002) Systems analysis of Ran transport. Science 295, 488-491
47. Nagai, M., Moriyama, T., Mehmood, R., Tokuhiro, K., Ikawa, M., Okabe, M., Tanaka, H., and Yoneda, Y. (2011) Mice lacking Ran binding protein 1 are viable and show male infertility. FEBS Lett. 585, 791-796
48. Delphin, C., Guan, T., Melchior, F., and Gerace, L. (1997) RanGTP targets p97 to RanBP2, a filamentous protein localized at the cytoplasmic periphery of the nuclear pore complex. Mol. Biol. Cell 8, 2379-2390
49. Bischoff, F. R., Krebber, H., Smirnova, E., Dong, W., and Ponstingl, H. (1995) Co-activation of RanGTPase and inhibition of GTP dissociation by Ran-GTP binding protein RanBP1. EMBO J. 14, 705-715
50. Vetter, I. R., Nowak, C., Nishimoto, T., Kuhlmann, J., and Wittinghofer, A. (1999) Structure of a Ran-binding domain complexed with Ran bound to a GTP analogue: implications for nuclear transport. Nature 398, 39-46
51. Izaurralde, E., Kutay, U., von Kobbe, C., Mattaj, I. W., and Görlich, D. (1997) The asymmetric distribution of the constituents of the Ran system is essential for transport into and out of the nucleus. EMBO J. 16, 6535-6547
52. Kaláb, P., Pralle, A., Isacoff, E. Y., Heald, R., and Weis, K. (2006) Analysis of a RanGTP-regulated gradient in mitotic somatic cells. Nature 440, 697-701
53. Carazo-Salas, R. E., Gruss, O. J., Mattaj, I. W., and Karsenti, E. (2001) Ran-GTP coordinates regulation of microtubule nucleation and dynamics during mitotic-spindle assembly. Nat. Cell Biol. 3, 228-234
54. Wilde, A., Lizarraga, S. B., Zhang, L., Wiese, C., Gliksman, N. R., Walczak, C. E., and Zheng, Y. (2001) Ran stimulates spindle assembly by altering microtubule dynamics and the balance of motor activities. Nat. Cell Biol. 3, 221-227
55. Clarke, P. R., and Zhang, C. (2008) Spatial and temporal coordination of mitosis by Ran GTPase. Nat. Rev. Mol. Cell Biol. 9, 464-477
56. Strambio-De-Castillia, C., Niepel, M., and Rout, M. P. (2010) The nuclear pore complex: bridging nuclear transport and gene regulation. Nat. Rev. Mol. Cell Biol. 11, 490-501
57. Joseph, J., Liu, S. T., Jablonski, S. A., Yen, T. J., and Dasso, M. (2004) The RanGAP1-RanBP2 complex is essential for microtubule-kinetochore interactions in vivo. Curr. Biol. 14, 611-617
58. Salina, D., Enarson, P., Rattner, J. B., and Burke, B. (2003) Nup358 integrates nuclear envelope breakdown with kinetochore assembly. J. Cell Biol. 162, 991-1001
59. Hashizume, C., Kobayashi, A., and Wong, R. W. (2013) Down-modulation of nucleoporin RanBP2/Nup358 impaired chromosomal alignment and induced mitotic catastrophe. Cell Death Dis. 4, e854
60. Hamada, M., Haeger, A., Jeganathan, K. B., van Ree, J. H., Malureanu, L., Wälde, S., Joseph, J., Kehlenbach, R. H., and van Deursen, J. M. (2011) Ran-dependent docking of importin-β to RanBP2/Nup358 filaments is essential for protein import and cell viability. J. Cell Biol. 194, 597-612
61. Wälde, S., Thakar, K., Hutten, S., Spillner, C., Nath, A., Rothbauer, U., Wiemann, S., and Kehlenbach, R. H. (2012) The nucleoporin Nup358/RanBP2 promotes nuclear import in a cargo- and transport receptor-specific manner. Traffic 13, 218-233
62. Walther, T. C., Pickersgill, H. S., Cordes, V. C., Goldberg, M. W., Allen, T. D., Mattaj, I. W., and Fornerod, M. (2002) The cytoplasmic filaments of the nuclear pore complex are dispensable for selective nuclear protein import. J. Cell Biol. 158, 63-77
63. Le, Y. Z., Zheng, W., Rao, P. C., Zheng, L., Anderson, R. E., Esumi, N., Zack, D. J., and Zhu, M. (2008) Inducible expression of cre recombinase in the retinal pigmented epithelium. Invest. Ophthalmol. Vis. Sci. 49, 1248-1253
64. Cho, K. I., Patil, H., Senda, E., Wang, J., Yi, H., Qiu, S., Yoon, D., Yu, M., Orry, A., Peachey, N. S., and Ferreira, P. A. (2014) Differential loss of prolyl isomerase or chaperone activity of Ran-binding protein 2 (Ranbp2) unveils distinct physiological roles of its cyclophilin domain in proteostasis. J. Biol. Chem. 289, 4600-4625
65. Yu, M., Sturgill-Short, G., Ganapathy, P., Tawfik, A., Peachey, N. S., and Smith, S. B. (2012) Age-related changes in visual function in cystathionine-β-synthase mutant mice, a model of hyperhomocysteinemia. Exp. Eye Res. 96, 124-131
66. Wu, J., Peachey, N. S., and Marmorstein, A. D. (2004) Light-evoked responses of the mouse retinal pigment epithelium. J. Neurophysiol. 91, 1134-1142
67. Petrukhin, K., Koisti, M. J., Bakall, B., Li, W., Xie, G., Marknell, T., Sandgren, O., Forsman, K., Holmgren, G., Andreasson, S., Vujic, M., Bergen, A. A., McGarty-Dugan, V., Figueroa, D., Austin, C. P., Metzker, M. L., Caskey, C. T., and Wadelius, C. (1998) Identification of the gene responsible for Best macular dystrophy. Nat. Genet. 19, 241-247
68. Fu, S., Zhu, M., Wang, C., and Le, Y. Z. (2014) Efficient induction of productive Cre-mediated recombination in retinal pigment epithelium. Mol. Vis. 20, 480-487
69. Ballestrem, C., Wehrle-Haller, B., and Imhof, B. A. (1998) Actin dynamics in living mammalian cells. J. Cell Sci. 111, 1649-1658
70. Kokkinopoulos, I., Shahabi, G., Colman, A., and Jeffery, G. (2011) Mature peripheral RPE cells have an intrinsic capacity to proliferate: a potential regulatory mechanism for age-related cell loss. PLoS One 6, e18921
71. Travis, G. H., Golczak, M., Moise, A. R., and Palczewski, K. (2007) Diseases caused by defects in the visual cycle: retinoids as potential therapeutic agents. Annu. Rev. Pharmacol. Toxicol. 47, 469-512
72. Westenskow, P., Piccolo, S., and Fuhrmann, S. (2009) β-Catenin controls differentiation of the retinal pigment epithelium in the mouse optic cup by regulating Mitf and Otx2 expression. Development 136, 2505-2510
73. Cai, H., Shin, M. C., Tezel, T. H., Kaplan, H. J., and Del Priore, L. V. (2006) Use of iris pigment epithelium to replace retinal pigment epithelium in age-related macular degeneration: a gene expression analysis. Arch. Ophthalmol. 124, 1276-1285
74. van Soest, S. S., de Wit, G. M., Essing, A. H., ten Brink, J. B., Kamphuis, W., de Jong, P. T., and Bergen, A. A. (2007) Comparison of human retinal pigment epithelium gene expression in macula and periphery highlights potential topographic differences in Bruch's membrane. Mol. Vis. 13, 1608-1617
75. Patel, A. K., Syeda, S., and Hackam, A. S. (2013) Signal transducer and activator of transcription 3 (STAT3) signaling in retinal pigment epithelium cells. Jakstat 2, e25434
76. Chucair-Elliott, A. J., Elliott, M. H., Wang, J., Moiseyev, G. P., Ma, J. X., Politi, L. E., Rotstein, N. P., Akira, S., Uematsu, S., and Ash, J. D. (2012) Leukemia inhibitory factor coordinates the down-regulation of the visual cycle in the retina and retinal-pigmented epithelium. J. Biol. Chem. 287, 24092-24102
77. Xu, K. P., and Yu, F. S. (2007) Cross talk between c-Met and epidermal growth factor receptor during retinal pigment epithelial wound healing. Invest. Ophthalmol. Vis. Sci. 48, 2242-2248
78. Fuchs, U., Kivelä, T., and Tarkkanen, A. (1991) Cytoskeleton in normal and reactive human retinal pigment epithelial cells. Invest. Ophthalmol. Vis. Sci. 32, 3178-3186
79. Singh, B. B., Patel, H. H., Roepman, R., Schick, D., and Ferreira, P. A. (1999) The zinc finger cluster domain of RanBP2 is a specific docking site for the nuclear export factor, exportin-1. J. Biol. Chem. 274, 37370-37378
80. Yi, H., Friedman, J. L., and Ferreira, P. A. (2007) The cyclophilin-like domain of Ran-binding protein-2 modulates selectively the activity of the ubiquitin-proteasome system and protein biogenesis. J. Biol. Chem. 282, 34770-34778
81. Giri, D. K., Ali-Seyed, M., Li, L. Y., Lee, D. F., Ling, P., Bartholomeusz, G., Wang, S. C., and Hung, M. C. (2005) Endosomal transport of ErbB-2: mechanism for nuclear entry of the cell surface receptor. Mol. Cell. Biol. 25, 11005-11018
82. Cai, Y., Singh, B. B., Aslanukov, A., Zhao, H., and Ferreira, P. A. (2001) The docking of kinesins, KIF5B and KIF5C, to Ran-binding protein 2 (RanBP2) is mediated via a novel RanBP2 domain. J. Biol. Chem. 276, 41594-41602
83. Cho, K. I., Cai, Y., Yi, H., Yeh, A., Aslanukov, A., and Ferreira, P. A. (2007) Association of the kinesin-binding domain of RanBP2 to KIF5B and KIF5C determines mitochondria localization and function. Traffic 8, 1722-1735
84. Cho, K. I., Yi, H., Desai, R., Hand, A. R., Haas, A. L., and Ferreira, P. A. (2009) RANBP2 is an allosteric activator of the conventional kinesin-1 motor protein, KIF5B, in a minimal cell-free system. EMBO Rep. 10, 480-486
85. Patil, H., Cho, K. I., Lee, J., Yang, Y., Orry, A., and Ferreira, P. A. (2013) Kinesin-1 and mitochondrial motility control by discrimination of structurally equivalent but distinct subdomains in Ran-GTP-binding domains of Ran-binding protein 2. Open Biol. 3, 120183
86. Samuels, I. S., Sturgill, G. M., Grossman, G. H., Rayborn, M. E., Hollyfield, J. G., and Peachey, N. S. (2010) Light-evoked responses of the retinal pigment epithelium: changes accompanying photoreceptor loss in the mouse. J. Neurophysiol. 104, 391-402
87. Duke-Elder, W. S., and Perkins, E. S. (1966) Systems of Ophthalmology, p. 675, C. V. Mosby Company, St. Louis
88. Rohrer, B., Spira, A. W., and Stell, W. K. (1993) Apomorphine blocks form-deprivation myopia in chickens by a dopamine D2-receptor mechanism acting in retina or pigmented epithelium. Vis. Neurosci. 10, 447-453
89. Nagai, M., and Yoneda, Y. (2013) Downregulation of the small GTPase ras-related nuclear protein accelerates cellular ageing. Biochim. Biophys. Acta 1830, 2813-2819
90. Kaylor, J. J., Yuan, Q., Cook, J., Sarfare, S., Makshanoff, J., Miu, A., Kim, A., Kim, P., Habib, S., Roybal, C. N., Xu, T., Nusinowitz, S., and Travis, G. H. (2013) Identification of DES1 as a vitamin A isomerase in Muller glial cells of the retina. Nat. Chem. Biol. 9, 30-36
91. Kaneko, H., Dridi, S., Tarallo, V., Gelfand, B. D., Fowler, B. J., Cho, W. G., Kleinman, M. E., Ponicsan, S. L., Hauswirth, W. W., Chiodo, V. A., Karikó, K., Yoo, J. W., Lee, D. K., Hadziahmetovic, M., Song, Y., Misra, S., Chaudhuri, G., Buaas, F. W., Braun, R. E., Hinton, D. R., Zhang, Q., Grossniklaus, H. E., Provis, J. M., Madigan, M. C., Milam, A. H., Justice, N. L., Albuquerque, R. J., Blandford, A. D., Bogdanovich, S., Hirano, Y., Witta, J., Fuchs, E., Littman, D. R., Ambati, B. K., Rudin, C. M., Chong, M. M., Provost, P., Kugel, J. F., Goodrich, J. A., Dunaief, J. L., Baffi, J. Z., and Ambati, J. (2011) DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration. Nature 471, 325-330
92. Marneros, A. G. (2013) NLRP3 inflammasome blockade inhibits VEGF-A-induced age-related macular degeneration. Cell Rep. 4, 945-958
93. Zhao, C., Yasumura, D., Li, X., Matthes, M., Lloyd, M., Nielsen, G., Ahern, K., Snyder, M., Bok, D., Dunaief, J. L., LaVail, M. M., and Vollrath, D. (2011) mTOR-mediated dedifferentiation of the retinal pigment epithelium initiates photoreceptor degeneration in mice. J. Clin. Invest. 121, 369-383
94. Longbottom, R., Fruttiger, M., Douglas, R. H., Martinez-Barbera, J. P., Greenwood, J., and Moss, S. E. (2009) Genetic ablation of retinal pigment epithelial cells reveals the adaptive response of the epithelium and impact on photoreceptors. Proc. Natl. Acad. Sci. U.S.A. 106, 18728-18733
95. Chiang, A. C., and Massagué, J. (2008) Molecular basis of metastasis. N. Engl. J. Med. 359, 2814-2823
96. Hanahan, D., and Weinberg, R. A. (2011) Hallmarks of cancer: the next generation. Cell 144, 646-674