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The Protein -glucosyltransferase Rumi Modifies Eyes Shut to Promote Rhabdomere Separation in


Glycosylation (addition of sugars to proteins and other organic molecules) is important for protein function and animal development. Each form of glycosylation is usually present on multiple proteins. Therefore, a major challenge in understanding the role of sugars in animal development is to identify which protein(s) modified by a specific sugar require the sugar modification for proper functionality. We have previously shown that an enzyme called Rumi adds glucose molecules to an important cell surface receptor called Notch, and that glucose plays a key role in the function of Notch both in fruit flies and in mammals. Using fruit flies, we have now identified a new Rumi target called “Eyes shut”, a secreted protein with a critical role in the optical isolation of neighboring photoreceptors in the fly eye. Our data suggest that glucose molecules on Eyes shut promote its folding and stability in a critical time window during eye development. Mutations in human Eyes shut result in a devastating form of retinal degeneration and loss of vision. Since human Eyes shut is also predicted to harbor glucose molecules, our work provides a framework to explore the role of sugar modifications in the biology of a human disease protein.


Vyšlo v časopise: The Protein -glucosyltransferase Rumi Modifies Eyes Shut to Promote Rhabdomere Separation in. PLoS Genet 10(11): e32767. doi:10.1371/journal.pgen.1004795
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004795

Souhrn

Glycosylation (addition of sugars to proteins and other organic molecules) is important for protein function and animal development. Each form of glycosylation is usually present on multiple proteins. Therefore, a major challenge in understanding the role of sugars in animal development is to identify which protein(s) modified by a specific sugar require the sugar modification for proper functionality. We have previously shown that an enzyme called Rumi adds glucose molecules to an important cell surface receptor called Notch, and that glucose plays a key role in the function of Notch both in fruit flies and in mammals. Using fruit flies, we have now identified a new Rumi target called “Eyes shut”, a secreted protein with a critical role in the optical isolation of neighboring photoreceptors in the fly eye. Our data suggest that glucose molecules on Eyes shut promote its folding and stability in a critical time window during eye development. Mutations in human Eyes shut result in a devastating form of retinal degeneration and loss of vision. Since human Eyes shut is also predicted to harbor glucose molecules, our work provides a framework to explore the role of sugar modifications in the biology of a human disease protein.


Zdroje

1. BorstA (2009) Drosophila's view on insect vision. Curr Biol 19: R36–47.

2. NilssonDE (1990) From cornea to retinal image in invertebrate eyes. Trends Neurosci 13: 55–64.

3. ClandininTR, ZipurskySL (2000) Afferent growth cone interactions control synaptic specificity in the Drosophila visual system. Neuron 28: 427–436.

4. KirschfeldK (1967) [The projection of the optical environment on the screen of the rhabdomere in the compound eye of the Musca] (Original in German). Exp Brain Res 3: 248–270.

5. HusainN, PellikkaM, HongH, KlimentovaT, ChoeKM, et al. (2006) The agrin/perlecan-related protein eyes shut is essential for epithelial lumen formation in the Drosophila retina. Dev Cell 11: 483–493.

6. ZelhofAC, HardyRW, BeckerA, ZukerCS (2006) Transforming the architecture of compound eyes. Nature 443: 696–699.

7. CoelhoDS, CairraoF, ZengX, PiresE, CoelhoAV, et al. (2013) Xbp1-independent Ire1 signaling is required for photoreceptor differentiation and rhabdomere morphogenesis in Drosophila. Cell Rep 5: 791–801.

8. GurudevN, YuanM, KnustE (2014) chaoptin, prominin, eyes shut and crumbs form a genetic network controlling the apical compartment of Drosophila photoreceptor cells. Biol Open 3: 332–341.

9. NieJ, MahatoS, MustillW, TippingC, BhattacharyaSS, et al. (2012) Cross species analysis of Prominin reveals a conserved cellular role in invertebrate and vertebrate photoreceptor cells. Dev Biol 371: 312–320.

10. TepassU, TheresC, KnustE (1990) crumbs encodes an EGF-like protein expressed on apical membranes of Drosophila epithelial cells and required for organization of epithelia. Cell 61: 787–799.

11. PellikkaM, TanentzapfG, PintoM, SmithC, McGladeCJ, et al. (2002) Crumbs, the Drosophila homologue of human CRB1/RP12, is essential for photoreceptor morphogenesis. Nature 416: 143–149.

12. AcarM, Jafar-NejadH, TakeuchiH, RajanA, IbraniD, et al. (2008) Rumi is a CAP10 domain glycosyltransferase that modifies Notch and is required for Notch signaling. Cell 132: 247–258.

13. RanaNA, Nita-LazarA, TakeuchiH, KakudaS, LutherKB, et al. (2011) O-glucose trisaccharide is present at high but variable stoichiometry at multiple sites on mouse Notch1. J Biol Chem 286: 31623–31637.

14. LeonardiJ, Fernandez-ValdiviaR, LiYD, SimcoxAA, Jafar-NejadH (2011) Multiple O-glucosylation sites on Notch function as a buffer against temperature-dependent loss of signaling. Development 138: 3569–3578.

15. PerdigotoCN, SchweisguthF, BardinAJ (2011) Distinct levels of Notch activity for commitment and terminal differentiation of stem cells in the adult fly intestine. Development 138: 4585–4595.

16. Fernandez-ValdiviaR, TakeuchiH, SamarghandiA, LopezM, LeonardiJ, et al. (2011) Regulation of the mammalian Notch signaling and embryonic development by the protein O-glucosyltransferase Rumi. Development 138: 1925–1934.

17. TakeuchiH, Fernandez-ValdiviaRC, CaswellDS, Nita-LazarA, RanaNA, et al. (2011) Rumi functions as both a protein O-glucosyltransferase and a protein O-xylosyltransferase. Proc Natl Acad Sci U S A 108: 16600–16605.

18. LeeTV, SethiMK, LeonardiL, RanaNA, BuettnerFF, et al. (2013) Negative Regulation of Notch Signaling by Xylose. PLoS Genet 9: e1003547.

19. LongleyRLJr, ReadyDF (1995) Integrins and the development of three-dimensional structure in the Drosophila compound eye. Dev Biol 171: 415–433.

20. IzaddoostS, NamSC, BhatMA, BellenHJ, ChoiKW (2002) Drosophila Crumbs is a positional cue in photoreceptor adherens junctions and rhabdomeres. Nature 416: 178–183.

21. JohnsonK, GraweF, GrzeschikN, KnustE (2002) Drosophila crumbs is required to inhibit light-induced photoreceptor degeneration. Curr Biol 12: 1675–1680.

22. ChenCL, GajewskiKM, HamaratogluF, BossuytW, Sansores-GarciaL, et al. (2010) The apical-basal cell polarity determinant Crumbs regulates Hippo signaling in Drosophila. Proc Natl Acad Sci U S A 107: 15810–15815.

23. LingC, ZhengY, YinF, YuJ, HuangJ, et al. (2010) The apical transmembrane protein Crumbs functions as a tumor suppressor that regulates Hippo signaling by binding to Expanded. Proc Natl Acad Sci U S A 107: 10532–10537.

24. RichardsonEC, PichaudF (2010) Crumbs is required to achieve proper organ size control during Drosophila head development. Development 137: 641–650.

25. HuangJ, ZhouW, DongW, WatsonAM, HongY (2009) From the Cover: Directed, efficient, and versatile modifications of the Drosophila genome by genomic engineering. Proc Natl Acad Sci U S A 106: 8284–8289.

26. RobinsonBS, HuangJ, HongY, MobergKH (2010) Crumbs regulates Salvador/Warts/Hippo signaling in Drosophila via the FERM-domain protein Expanded. Curr Biol 20: 582–590.

27. RyooHD, DomingosPM, KangMJ, StellerH (2007) Unfolded protein response in a Drosophila model for retinal degeneration. Embo J 26: 242–252.

28. BischofJ, MaedaRK, HedigerM, KarchF, BaslerK (2007) An optimized transgenesis system for Drosophila using germ-line-specific phiC31 integrases. Proc Natl Acad Sci U S A 104: 3312–3317.

29. VenkenKJ, HeY, HoskinsRA, BellenHJ (2006) P[acman]: a BAC transgenic platform for targeted insertion of large DNA fragments in D. melanogaster. Science 314: 1747–1751.

30. MoloneyDJ, ShairLH, LuFM, XiaJ, LockeR, et al. (2000) Mammalian Notch1 is modified with two unusual forms of O-linked glycosylation found on epidermal growth factor-like modules. J Biol Chem 275: 9604–9611.

31. TakeuchiH, KanthariaJ, SethiMK, BakkerH, HaltiwangerRS (2012) Site-specific O-glucosylation of the epidermal growth factor-like (EGF) repeats of notch: efficiency of glycosylation is affected by proper folding and amino acid sequence of individual EGF repeats. J Biol Chem 287: 33934–33944.

32. WodarzA, HinzU, EngelbertM, KnustE (1995) Expression of crumbs confers apical character on plasma membrane domains of ectodermal epithelia of Drosophila. Cell 82: 67–76.

33. RoperK (2012) Anisotropy of Crumbs and aPKC drives myosin cable assembly during tube formation. Developmental cell 23: 939–953.

34. Abd El-AzizMM, BarraganI, O'DriscollCA, GoodstadtL, PrigmoreE, et al. (2008) EYS, encoding an ortholog of Drosophila spacemaker, is mutated in autosomal recessive retinitis pigmentosa. Nat Genet 40: 1285–1287.

35. CollinRW, LittinkKW, KleveringBJ, van den BornLI, KoenekoopRK, et al. (2008) Identification of a 2 Mb human ortholog of Drosophila eyes shut/spacemaker that is mutated in patients with retinitis pigmentosa. Am J Hum Genet 83: 594–603.

36. IwanamiM, OshikawaM, NishidaT, NakadomariS, KatoS (2012) High prevalence of mutations in the EYS gene in Japanese patients with autosomal recessive retinitis pigmentosa. Invest Ophthalmol Vis Sci 53: 1033–1040.

37. LittinkKW, van den BornLI, KoenekoopRK, CollinRW, ZonneveldMN, et al. (2010) Mutations in the EYS gene account for approximately 5% of autosomal recessive retinitis pigmentosa and cause a fairly homogeneous phenotype. Ophthalmology 117: 2026–2027, 2026-2033, 2033, e2021-2027.

38. AudoI, SahelJA, Mohand-SaidS, LancelotME, AntonioA, et al. (2010) EYS is a major gene for rod-cone dystrophies in France. Hum Mutat 31: E1406–1435.

39. KatagiriS, AkahoriM, HayashiT, YoshitakeK, GekkaT, et al. (2014) Autosomal recessive cone-rod dystrophy associated with compound heterozygous mutations in the EYS gene. Doc Ophthalmol 128: 211–217.

40. PrasE, AbuA, RotenstreichY, AvniI, ReishO, et al. (2009) Cone-rod dystrophy and a frameshift mutation in the PROM1 gene. Mol Vis 15: 1709–1716.

41. ZhangQ, ZulfiqarF, XiaoX, RiazuddinSA, AhmadZ, et al. (2007) Severe retinitis pigmentosa mapped to 4p15 and associated with a novel mutation in the PROM1 gene. Hum Genet 122: 293–299.

42. BeryozkinA, ZelingerL, Bandah-RozenfeldD, ShevachE, HarelA, et al. (2014) Identification of mutations causing inherited retinal degenerations in the israeli and palestinian populations using homozygosity mapping. Invest Ophthalmol Vis Sci 55: 1149–1160.

43. PermanyerJ, NavarroR, FriedmanJ, PomaresE, Castro-NavarroJ, et al. (2010) Autosomal recessive retinitis pigmentosa with early macular affectation caused by premature truncation in PROM1. Invest Ophthalmol Vis Sci 51: 2656–2663.

44. XuD, WangY, WilleckeR, ChenZ, DingT, et al. (2006) The effector caspases drICE and dcp-1 have partially overlapping functions in the apoptotic pathway in Drosophila. Cell death and differentiation 13: 1697–1706.

45. OkajimaT, XuA, IrvineKD (2003) Modulation of notch-ligand binding by protein O-fucosyltransferase 1 and fringe. J Biol Chem 278: 42340–42345.

46. XuA, HainesN, DlugoszM, RanaNA, TakeuchiH, et al. (2007) In vitro reconstitution of the modulation of Drosophila Notch-ligand binding by Fringe. J Biol Chem 282: 35153–35162.

47. Nita-LazarA, HaltiwangerRS (2006) Methods for analysis of O-linked modifications on epidermal growth factor-like and thrombospondin type 1 repeats. Methods Enzymol 417: 93–111.

48. CuliJ, MannRS (2003) Boca, an endoplasmic reticulum protein required for wingless signaling and trafficking of LDL receptor family members in Drosophila. Cell 112: 343–354.

49. SissonJC, FieldC, VenturaR, RoyouA, SullivanW (2000) Lava lamp, a novel peripheral golgi protein, is required for Drosophila melanogaster cellularization. J Cell Biol 151: 905–918.

50. SatohAK, O'TousaJE, OzakiK, ReadyDF (2005) Rab11 mediates post-Golgi trafficking of rhodopsin to the photosensitive apical membrane of Drosophila photoreceptors. Development 132: 1487–1497.

51. ChinchoreY, MitraA, DolphPJ (2009) Accumulation of rhodopsin in late endosomes triggers photoreceptor cell degeneration. PLoS Genet 5: e1000377.

52. NoloR, AbbottLA, BellenHJ (2000) Senseless, a Zn finger transcription factor, is necessary and sufficient for sensory organ development in Drosophila. Cell 102: 349–362.

53. Fabian-FineR, VerstrekenP, HiesingerPR, HorneJA, KostylevaR, et al. (2003) Endophilin promotes a late step in endocytosis at glial invaginations in Drosophila photoreceptor terminals. J Neurosci 23: 10732–10744.

54. SiegalML, HartlDL (1996) Transgene Coplacement and high efficiency site-specific recombination with the Cre/loxP system in Drosophila. Genetics 144: 715–726.

55. HiguchiR, KrummelB, SaikiRK (1988) A general method of in vitro preparation and specific mutagenesis of DNA fragments: study of protein and DNA interactions. Nucleic Acids Res 16: 7351–7367.

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