Suppression of retinal degeneration by two novel ERAD ubiquitin E3 ligases SORDD1/2 in Drosophila


Autoři: Jaiwei Xu aff001;  Haifang Zhao aff002;  Tao Wang aff002
Působiště autorů: College of Biological Sciences, China Agricultural University, China aff001;  National Institute of Biological Sciences, China aff002;  Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, China aff003
Vyšlo v časopise: Suppression of retinal degeneration by two novel ERAD ubiquitin E3 ligases SORDD1/2 in Drosophila. PLoS Genet 16(11): e32767. doi:10.1371/journal.pgen.1009172
Kategorie: Research Article
doi: 10.1371/journal.pgen.1009172

Souhrn

Mutations in the gene rhodopsin are one of the major causes of autosomal dominant retinitis pigmentosa (adRP). Mutant forms of Rhodopsin frequently accumulate in the endoplasmic reticulum (ER), cause ER stress, and trigger photoreceptor cell degeneration. Here, we performed a genome-wide screen to identify suppressors of retinal degeneration in a Drosophila model of adRP, carrying a point mutation in the major rhodopsin, Rh1 (Rh1G69D). We identified two novel E3 ubiquitin ligases SORDD1 and SORDD2 that effectively suppressed Rh1G69D-induced photoreceptor dysfunction and retinal degeneration. SORDD1/2 promoted the ubiquitination and degradation of Rh1G69D through VCP (valosin containing protein) and independent of processes reliant on the HRD1 (HMG-CoA reductase degradation protein 1)/HRD3 complex. We further demonstrate that SORDD1/2 and HRD1 function in parallel and in a redundant fashion to maintain rhodopsin homeostasis and integrity of photoreceptor cells. These findings identify a new ER-associated protein degradation (ERAD) pathway and suggest that facilitating SORDD1/2 function may be a therapeutic strategy to treat adRP.

Klíčová slova:

Endoplasmic reticulum – Eyes – Homeostasis – Ligases – Photoreceptors – Proteasomes – Retinal degeneration – Ubiquitin ligases


Zdroje

1. Sullivan LS, Bowne SJ, Birch DG, Hughbanks-Wheaton D, Heckenlively JR, Lewis RA, et al. Prevalence of disease-causing mutations in families with autosomal dominant retinitis pigmentosa: a screen of known genes in 200 families. Invest Ophthalmol Vis Sci. 2006;47(7):3052–64. Epub 2006/06/27. doi: 10.1167/iovs.05-1443 16799052; PubMed Central PMCID: PMC2585061.

2. Dryja TP, McGee TL, Reichel E, Hahn LB, Cowley GS, Yandell DW, et al. A point mutation of the rhodopsin gene in one form of retinitis pigmentosa. Nature. 1990;343(6256):364–6. Epub 1990/01/25. doi: 10.1038/343364a0 2137202.

3. Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa. Lancet. 2006;368(9549):1795–809. Epub 2006/11/23. doi: 10.1016/S0140-6736(06)69740-7 17113430.

4. Mendes HF, van der Spuy J, Chapple JP, Cheetham ME. Mechanisms of cell death in rhodopsin retinitis pigmentosa: implications for therapy. Trends Mol Med. 2005;11(4):177–85. Epub 2005/04/13. doi: 10.1016/j.molmed.2005.02.007 15823756.

5. Lin JH, Li H, Yasumura D, Cohen HR, Zhang C, Panning B, et al. IRE1 signaling affects cell fate during the unfolded protein response. Science. 2007;318(5852):944–9. Epub 2007/11/10. doi: 10.1126/science.1146361 17991856; PubMed Central PMCID: PMC3670588.

6. Sung CH, Davenport CM, Hennessey JC, Maumenee IH, Jacobson SG, Heckenlively JR, et al. Rhodopsin mutations in autosomal dominant retinitis pigmentosa. Proc Natl Acad Sci U S A. 1991;88(15):6481–5. Epub 1991/08/01. doi: 10.1073/pnas.88.15.6481 1862076; PubMed Central PMCID: PMC52109.

7. Athanasiou D, Kosmaoglou M, Kanuga N, Novoselov SS, Paton AW, Paton JC, et al. BiP prevents rod opsin aggregation. Mol Biol Cell. 2012;23(18):3522–31. Epub 2012/08/03. doi: 10.1091/mbc.E12-02-0168 22855534; PubMed Central PMCID: PMC3442401.

8. Sakami S, Maeda T, Bereta G, Okano K, Golczak M, Sumaroka A, et al. 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. 2011;286(12):10551–67. Epub 2011/01/13. doi: 10.1074/jbc.M110.209759 21224384; PubMed Central PMCID: PMC3060508.

9. Meusser B, Hirsch C, Jarosch E, Sommer T. ERAD: the long road to destruction. Nat Cell Biol. 2005;7(8):766–72. Epub 2005/08/02. doi: 10.1038/ncb0805-766 16056268.

10. Vembar SS, Brodsky JL. One step at a time: endoplasmic reticulum-associated degradation. Nat Rev Mol Cell Biol. 2008;9(12):944–57. Epub 2008/11/13. doi: 10.1038/nrm2546 19002207; PubMed Central PMCID: PMC2654601.

11. Huang HW, Brown B, Chung J, Domingos PM, Ryoo HD. highroad Is a Carboxypetidase Induced by Retinoids to Clear Mutant Rhodopsin-1 in Drosophila Retinitis Pigmentosa Models. Cell Rep. 2018;22(6):1384–91. Epub 2018/02/10. doi: 10.1016/j.celrep.2018.01.032 29425495; PubMed Central PMCID: PMC5832065.

12. Walter P, Ron D. The unfolded protein response: from stress pathway to homeostatic regulation. Science. 2011;334(6059):1081–6. Epub 2011/11/26. doi: 10.1126/science.1209038 22116877.

13. Chiang WC, Messah C, Lin JH. IRE1 directs proteasomal and lysosomal degradation of misfolded rhodopsin. Mol Biol Cell. 2012;23(5):758–70. Epub 2012/01/06. doi: 10.1091/mbc.E11-08-0663 22219383; PubMed Central PMCID: PMC3290636.

14. Athanasiou D, Aguila M, Bellingham J, Kanuga N, Adamson P, Cheetham ME. The role of the ER stress-response protein PERK in rhodopsin retinitis pigmentosa. Hum Mol Genet. 2017;26(24):4896–905. Epub 2017/10/17. doi: 10.1093/hmg/ddx370 29036441; PubMed Central PMCID: PMC5868081.

15. Chiang W-C, Kroeger H, Sakami S, Messah C, Yasumura D, Matthes MT, et al. Robust Endoplasmic Reticulum-Associated Degradation of Rhodopsin Precedes Retinal Degeneration. Mol Neurobiol. 2015;52(1):679–95. Epub 2014/10/02. doi: 10.1007/s12035-014-8881-8 25270370.

16. Xiong L, Zhang L, Yang Y, Li N, Lai W, Wang F, et al. ER complex proteins are required for rhodopsin biosynthesis and photoreceptor survival in Drosophila and mice. Cell Death Differ. 2020;27(2):646–61. Epub 2019/07/03. doi: 10.1038/s41418-019-0378-6 31263175.

17. Lobanova ES, Finkelstein S, Skiba NP, Arshavsky VY. Proteasome overload is a common stress factor in multiple forms of inherited retinal degeneration. Proc Natl Acad Sci U S A. 2013;110(24):9986–91. Epub 2013/05/30. doi: 10.1073/pnas.1305521110 23716657; PubMed Central PMCID: PMC3683722.

18. Lobanova ES, Finkelstein S, Li J, Travis AM, Hao Y, Klingeborn M, et al. Increased proteasomal activity supports photoreceptor survival in inherited retinal degeneration. Nat Commun. 2018;9(1):1738. Epub 2018/05/02. doi: 10.1038/s41467-018-04117-8 29712894; PubMed Central PMCID: PMC5928105.

19. Kang MJ, Ryoo HD. Suppression of retinal degeneration in Drosophila by stimulation of ER-associated degradation. Proc Natl Acad Sci U S A. 2009;106(40):17043–8. Epub 2009/10/07. doi: 10.1073/pnas.0905566106 19805114; PubMed Central PMCID: PMC2749843.

20. Kurada P, O'Tousa JE. Retinal degeneration caused by dominant rhodopsin mutations in Drosophila. Neuron. 1995;14(3):571–9. Epub 1995/03/01. doi: 10.1016/0896-6273(95)90313-5 7695903.

21. Colley NJ, Cassill JA, Baker EK, Zuker CS. Defective intracellular transport is the molecular basis of rhodopsin-dependent dominant retinal degeneration. Proc Natl Acad Sci U S A. 1995;92(7):3070–4. Epub 1995/03/28. doi: 10.1073/pnas.92.7.3070 7708777; PubMed Central PMCID: PMC42361.

22. Bischof J, Sheils EM, Bjorklund M, Basler K. Generation of a transgenic ORFeome library in Drosophila. Nat Protoc. 2014;9(7):1607–20. Epub 2014/06/13. doi: 10.1038/nprot.2014.105 24922270; PubMed Central PMCID: PMC4150248.

23. Kaneko M, Iwase I, Yamasaki Y, Takai T, Wu Y, Kanemoto S, et al. Genome-wide identification and gene expression profiling of ubiquitin ligases for endoplasmic reticulum protein degradation. Sci Rep. 2016;6(1):30955. Epub 2016/08/04. doi: 10.1038/srep30955 27485036; PubMed Central PMCID: PMC4971459.

24. Griciuc A, Aron L, Piccoli G, Ueffing M. Clearance of Rhodopsin(P23H) aggregates requires the ERAD effector VCP. Biochim Biophys Acta. 2010;1803(3):424–34. Epub 2010/01/26. doi: 10.1016/j.bbamcr.2010.01.008 20097236.

25. El Khouri E, Le Pavec G, Toledano MB, Delaunay-Moisan A. RNF185 is a novel E3 ligase of endoplasmic reticulum-associated degradation (ERAD) that targets cystic fibrosis transmembrane conductance regulator (CFTR). J Biol Chem. 2013;288(43):31177–91. Epub 2013/09/11. doi: 10.1074/jbc.M113.470500 24019521; PubMed Central PMCID: PMC3829429.

26. van de Weijer ML, Krshnan L, Liberatori S, Guerrero EN, Robson-Tull J, Hahn L, et al. Quality Control of ER Membrane Proteins by the RNF185/Membralin Ubiquitin Ligase Complex. Mol Cell. 2020. Epub 2020/08/02. doi: 10.1016/j.molcel.2020.07.009 32738194.

27. Kang MJ, Chung J, Ryoo HD. CDK5 and MEKK1 mediate pro-apoptotic signalling following endoplasmic reticulum stress in an autosomal dominant retinitis pigmentosa model. Nat Cell Biol. 2012;14(4):409–15. Epub 2012/03/06. doi: 10.1038/ncb2447 22388889; PubMed Central PMCID: PMC3319494.

28. Nakatsukasa K, Brodsky JL. The recognition and retrotranslocation of misfolded proteins from the endoplasmic reticulum. Traffic. 2008;9(6):861–70. Epub 2008/03/05. doi: 10.1111/j.1600-0854.2008.00729.x 18315532; PubMed Central PMCID: PMC2754126.

29. Baldridge RD, Rapoport TA. Autoubiquitination of the Hrd1 Ligase Triggers Protein Retrotranslocation in ERAD. Cell. 2016;166(2):394–407. Epub 2016/06/21. doi: 10.1016/j.cell.2016.05.048 27321670; PubMed Central PMCID: PMC4946995.

30. Schoebel S, Mi W, Stein A, Ovchinnikov S, Pavlovicz R, DiMaio F, et al. Cryo-EM structure of the protein-conducting ERAD channel Hrd1 in complex with Hrd3. Nature. 2017;548(7667):352–5. Epub 2017/07/07. doi: 10.1038/nature23314 28682307; PubMed Central PMCID: PMC5736104.

31. Mishra M, Knust E. Analysis of the Drosophila Compound Eye with Light and Electron Microscopy: Methods and Protocols. 18342019. p. 345–64.

32. Wang T, Montell C. Phototransduction and retinal degeneration in Drosophila. Pflugers Arch. 2007;454(5):821–47. Epub 2007/05/10. doi: 10.1007/s00424-007-0251-1 17487503.

33. Ploegh HL. A lipid-based model for the creation of an escape hatch from the endoplasmic reticulum. Nature. 2007;448(7152):435–8. Epub 2007/07/27. doi: 10.1038/nature06004 17653186.

34. Oyadomari S, Yun C, Fisher EA, Kreglinger N, Kreibich G, Oyadomari M, et al. Cotranslocational degradation protects the stressed endoplasmic reticulum from protein overload. Cell. 2006;126(4):727–39. Epub 2006/08/23. doi: 10.1016/j.cell.2006.06.051 16923392.

35. Xiong B, Bellen HJ. Rhodopsin homeostasis and retinal degeneration: lessons from the fly. Trends Neurosci. 2013;36(11):652–60. Epub 2013/09/10. doi: 10.1016/j.tins.2013.08.003 24012059; PubMed Central PMCID: PMC3955215.

36. Mohlin C, Taylor L, Ghosh F, Johansson K. Autophagy and ER-stress contribute to photoreceptor degeneration in cultured adult porcine retina. Brain Res. 2014;1585:167–83. doi: 10.1016/j.brainres.2014.08.055 25173074

37. Midorikawa R, Yamamoto-Hino M, Awano W, Hinohara Y, Suzuki E, Ueda R, et al. Autophagy-dependent rhodopsin degradation prevents retinal degeneration in Drosophila. J Neurosci. 2010;30(32):10703–19. Epub 2010/08/13. doi: 10.1523/JNEUROSCI.2061-10.2010 20702701; PubMed Central PMCID: PMC6634698.

38. Yao J, Qiu Y, Frontera E, Jia L, Khan NW, Klionsky DJ, et al. Inhibiting autophagy reduces retinal degeneration caused by protein misfolding. Autophagy. 2018;14(7):1226–38. Epub 2018/07/13. doi: 10.1080/15548627.2018.1463121 29940785.

39. Gorbatyuk MS, Knox T, LaVail MM, Gorbatyuk OS, Noorwez SM, Hauswirth WW, et al. Restoration of visual function in P23H rhodopsin transgenic rats by gene delivery of BiP/Grp78. Proc Natl Acad Sci U S A. 2010;107(13):5961–6. Epub 2010/03/17. doi: 10.1073/pnas.0911991107 20231467; PubMed Central PMCID: PMC2851865.

40. Wei J, Yuan Y, Chen L, Xu Y, Zhang Y, Wang Y, et al. ER-associated ubiquitin ligase HRD1 programs liver metabolism by targeting multiple metabolic enzymes. Nat Commun. 2018;9(1):3659. Epub 2018/09/12. doi: 10.1038/s41467-018-06091-7 30201971; PubMed Central PMCID: PMC6131148.

41. Fernandez-Sanchez L, Bravo-Osuna I, Lax P, Arranz-Romera A, Maneu V, Esteban-Perez S, et al. Controlled delivery of tauroursodeoxycholic acid from biodegradable microspheres slows retinal degeneration and vision loss in P23H rats. PLoS One. 2017;12(5):e0177998. Epub 2017/05/26. doi: 10.1371/journal.pone.0177998 28542454; PubMed Central PMCID: PMC5444790.

42. Sakami S, Kolesnikov AV, Kefalov VJ, Palczewski K. P23H opsin knock-in mice reveal a novel step in retinal rod disc morphogenesis. Hum Mol Genet. 2014;23(7):1723–41. Epub 2013/11/07. doi: 10.1093/hmg/ddt561 24214395

43. Ju J-S, Fuentealba RA, Miller SE, Jackson E, Piwnica-Worms D, Baloh RH, et al. Valosin-containing protein (VCP) is required for autophagy and is disrupted in VCP disease. J Cell Biol. 2009;187(6):875–88. doi: 10.1083/jcb.200908115 20008565

44. Qiu Y, Yao J, Jia L, Thompson DA, Zacks DN. Shifting the balance of autophagy and proteasome activation reduces proteotoxic cell death: a novel therapeutic approach for restoring photoreceptor homeostasis. Cell Death Dis. 2019;10(8):547–. doi: 10.1038/s41419-019-1780-1 31320609.

45. Tyler RE, Pearce MM, Shaler TA, Olzmann JA, Greenblatt EJ, Kopito RR. Unassembled CD147 is an endogenous endoplasmic reticulum-associated degradation substrate. Mol Biol Cell. 2012;23(24):4668–78. Epub 2012/10/26. doi: 10.1091/mbc.E12-06-0428 23097496; PubMed Central PMCID: PMC3521676.

46. Sun S, Shi G, Sha H, Ji Y, Han X, Shu X, et al. IRE1alpha is an endogenous substrate of endoplasmic-reticulum-associated degradation. Nat Cell Biol. 2015;17(12):1546–55. Epub 2015/11/10. doi: 10.1038/ncb3266 26551274; PubMed Central PMCID: PMC4670240.

47. Morito D, Hirao K, Oda Y, Hosokawa N, Tokunaga F, Cyr DM, et al. Gp78 Cooperates with RMA1 in Endoplasmic Reticulum-associated Degradation of CFTRΔF508. Mol Biol Cell. 2008;19(4):1328–36. doi: 10.1091/mbc.e07-06-0601 18216283

48. Sondo E, Falchi F, Caci E, Ferrera L, Giacomini E, Pesce E, et al. Pharmacological Inhibition of the Ubiquitin Ligase RNF5 Rescues F508del-CFTR in Cystic Fibrosis Airway Epithelia. Cell Chemical Biology. 2018;25(7):891–905.e8. doi: 10.1016/j.chembiol.2018.04.010 29754957

49. Tomati V, Sondo E, Armirotti A, Caci E, Pesce E, Marini M, et al. Genetic Inhibition Of The Ubiquitin Ligase Rnf5 Attenuates Phenotypes Associated To F508del Cystic Fibrosis Mutation. Sci Rep. 2015;5:12138–. doi: 10.1038/srep12138 26183966.

50. Ryoo HD, Domingos PM, Kang MJ, Steller H. Unfolded protein response in a Drosophila model for retinal degeneration. EMBO J. 2007;26(1):242–52. Epub 2006/12/16. doi: 10.1038/sj.emboj.7601477 17170705; PubMed Central PMCID: PMC1782370.

51. Xu Y, An F, Borycz JA, Borycz J, Meinertzhagen IA, Wang T. Histamine Recycling Is Mediated by CarT, a Carcinine Transporter in Drosophila Photoreceptors. PLoS Genet. 2015;11(12):e1005764. Epub 2015/12/30. doi: 10.1371/journal.pgen.1005764 26713872; PubMed Central PMCID: PMC4694695.

52. Xu Y, Wang T. CULD is required for rhodopsin and TRPL channel endocytic trafficking and survival of photoreceptor cells. J Cell Sci. 2016;129(2):394–405. Epub 2015/11/26. doi: 10.1242/jcs.178764 26598556; PubMed Central PMCID: PMC4732287.

53. Zhao H, Wang J, Wang T. The V-ATPase V1 subunit A1 is required for rhodopsin anterograde trafficking in Drosophila. Mol Biol Cell. 2018;29(13):1640–51. Epub 2018/05/10. doi: 10.1091/mbc.E17-09-0546 29742016; PubMed Central PMCID: PMC6080656.

54. Hudson AM, Mannix KM, Cooley L. Actin Cytoskeletal Organization in Drosophila Germline Ring Canals Depends on Kelch Function in a Cullin-RING E3 Ligase. Genetics. 2015;201(3):1117–31. Epub 2015/09/19. doi: 10.1534/genetics.115.181289 26384358; PubMed Central PMCID: PMC4649639.


Článek vyšel v časopise

PLOS Genetics


2020 Číslo 11

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…


Přihlášení
Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se