In vivo expression of peptidylarginine deiminase in Drosophila melanogaster

English version

Autoři: Olena Mahneva ^aff001; Monica G. Risley ^aff001; Ciny John ^aff001; Sarah L. Milton ^aff001; Ken Dawson-Scully ^aff001; William W. Ja ^aff003
Působiště autorů: Department of Biological Sciences, Florida Atlantic University, Boca Raton, Florida, United States of America ^aff001; International Max Planck Research School (IMPRS) for Brain and Behavior, Boca Raton, Florida, United States of America ^aff002; Department of Neuroscience, The Scripps Research Institute, Jupiter, Florida, United States of America ^aff003; Center on Aging, The Scripps Research Institute, Jupiter, Florida, United States of America ^aff004
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0227822

Souhrn

Peptidylarginine deiminase (PAD) modifies peptidylarginine and converts it to peptidylcitrulline in the presence of elevated calcium. Protein modification can lead to severe changes in protein structure and function, and aberrant PAD activity is linked to human pathologies. While PAD homologs have been discovered in vertebrates—as well as in protozoa, fungi, and bacteria—none have been identified in Drosophila melanogaster, a simple and widely used animal model for human diseases. Here, we describe the development of a human PAD overexpression model in Drosophila. We established fly lines harboring human PAD2 or PAD4 transgenes for ectopic expression under control of the GAL4/UAS system. We show that ubiquitous or nervous system expression of PAD2 or PAD4 have minimal impact on fly lifespan, fecundity, and the response to acute heat stress. Although we did not detect citrullinated proteins in fly homogenates, fly-expressed PAD4—but not PAD2—was active in vitro upon Ca²⁺ supplementation. The transgenic fly lines may be valuable in future efforts to develop animal models of PAD-related disorders and for investigating the biochemistry and regulation of PAD function.

Klíčová slova:

Biological locomotion – Drosophila melanogaster – Fecundity – Heat treatment – Hyperthermia – Protein extraction – Thermal stresses – Citrullination

Zdroje

1. Fujisaki M, Sugawara K (1981) Properties of peptidylarginine deiminase from the epidermis of newborn rats. J Biochem 89: 257–263. doi: 10.1093/oxfordjournals.jbchem.a133189 7217033

2. Arita K, Hashimoto H, Shimizu T, Nakashima K, Yamada M, et al. (2004) Structural basis for Ca(2+)-induced activation of human PAD4. Nat Struct Mol Biol 11: 777–783. doi: 10.1038/nsmb799 15247907

3. Guo Q, Fast W (2011) Citrullination of inhibitor of growth 4 (ING4) by peptidylarginine deminase 4 (PAD4) disrupts the interaction between ING4 and p53. J Biol Chem 286: 17069–17078. doi: 10.1074/jbc.M111.230961 21454715

4. Kan R, Jin M, Subramanian V, Causey CP, Thompson PR, et al. (2012) Potential role for PADI-mediated histone citrullination in preimplantation development. BMC Dev Biol 12: 19. doi: 10.1186/1471-213X-12-19 22712504

5. Chavanas S, Mechin MC, Takahara H, Kawada A, Nachat R, et al. (2004) Comparative analysis of the mouse and human peptidylarginine deiminase gene clusters reveals highly conserved non-coding segments and a new human gene, PADI6. Gene 330: 19–27. doi: 10.1016/j.gene.2003.12.038 15087120

6. Shimizu A, Handa K, Honda T, Abe N, Kojima T, et al. (2014) Three isozymes of peptidylarginine deiminase in the chicken: molecular cloning, characterization, and tissue distribution. Comp Biochem Physiol B Biochem Mol Biol 167: 65–73. doi: 10.1016/j.cbpb.2013.10.003 24161753

7. Takahara H, Okamoto H, Sugawara K (1986) Calcium-dependent Properties of Peptidylarginine Deiminase from Rabbit Skeletal Muscle. Agricultural and Biological Chemistry 50: 2899–2904.

8. Rebl A, Köllner B, Anders E, Wimmers K, Goldammer T. Peptidylarginine deiminase gene is differentially expressed in freshwater and brackish water rainbow trout. Mol Biol Rep. 2010;37: 2333–2339. doi: 10.1007/s11033-009-9738-5 19693695

9. Magnadóttir B, Hayes P, Hristova M, Bragason BT, Nicholas AP, Dodds AW, et al. Post-translational protein deimination in cod (Gadus morhua L.) ontogeny novel roles in tissue remodelling and mucosal immune defences? Dev Comp Immunol. 2018;87: 157–170. doi: 10.1016/j.dci.2018.06.006 29908202

10. Magnadóttir B, Bragason BT, Bricknell IR, Bowden T, Nicholas AP, Hristova M, et al. Peptidylarginine deiminase and deiminated proteins are detected throughout early halibut ontogeny—Complement components C3 and C4 are post-translationally deiminated in halibut (Hippoglossus hippoglossus L.). Dev Comp Immunol. 2019;92: 1–19. doi: 10.1016/j.dci.2018.10.016 30395876

11. Criscitiello MF, Kraev I, Lange S. Deiminated proteins in extracellular vesicles and plasma of nurse shark (Ginglymostoma cirratum)—Novel insights into shark immunity. Fish Shellfish Immunol. 2019;92: 249–255. doi: 10.1016/j.fsi.2019.06.012 31200072

12. Touz MC, Rópolo AS, Rivero MR, Vranych CV, Conrad JT, Svard SG, et al. Arginine deiminase has multiple regulatory roles in the biology of Giardia lamblia. J Cell Sci. 2008;121: 2930–2938. doi: 10.1242/jcs.026963 18697833

13. Vranych C V., Rivero MR, Merino MC, Mayol GF, Zamponi N, Maletto BA, et al. SUMOylation and deimination of proteins: Two epigenetic modifications involved in Giardia encystation. Biochim Biophys Acta—Mol Cell Res. 2014;1843: 1805–1817.

14. El-Sayed ASA, Shindia AA, AbouZaid AA, Yassin AM, Ali GS, Sitohy MZ. Biochemical characterization of peptidylarginine deiminase-like orthologs from thermotolerant Emericella dentata and Aspergillus nidulans. Enzyme Microb Technol. 2019;124: 41–53. doi: 10.1016/j.enzmictec.2019.02.004 30797478

15. Bielecka E, Scavenius C, Kantyka T, Jusko M, Mizgalska D, Szmigielski B, et al. Peptidyl arginine deiminase from porphyromonas gingivalis abolishes anaphylatoxin C5a activity. J Biol Chem. 2014;289: 32481–32487. doi: 10.1074/jbc.C114.617142 25324545

16. Bereta G, Goulas T, Madej M, Bielecka E, Solà M, Potempa J, et al. Structure, function, and inhibition of a genomic/clinical variant of Porphyromonas gingivalis peptidylarginine deiminase. Protein Sci. 2019;28: 478–486. doi: 10.1002/pro.3571 30638292

17. Kosgodage US, Matewele P, Mastroianni G, Kraev I, Brotherton D, Awamaria B, et al. Peptidylarginine deiminase inhibitors reduce bacterial membrane vesicle release and sensitize bacteria to antibiotic treatment. Front Cell Infect Microbiol. 2019;9.

18. Christophorou MA, Castelo-Branco G, Halley-Stott RP, Oliveira CS, Loos R, Radzisheuskaya A, et al. Citrullination regulates pluripotency and histone H1 binding to chromatin. Nature. 2014;507: 104–108. doi: 10.1038/nature12942 24463520

19. Wang Y, Wysocka J, Sayegh J, Lee YH, Pertin JR, Leonelli L, et al. Human PAD4 regulates histone arginine methylation levels via demethylimination. Science (80-). 2004;306: 279–283.

20. Kholia S, Jorfi S, Thompson PR, Causey CP, Nicholas AP, et al. (2015) A novel role for peptidylarginine deiminases in microvesicle release reveals therapeutic potential of PAD inhibition in sensitizing prostate cancer cells to chemotherapy. J Extracell Vesicles 4: 26192. doi: 10.3402/jev.v4.26192 26095379

21. Gavinho B, Rossi IV, Evans-Osses I, Lange S, Ramirez MI (2019) Peptidylarginine deiminase inhibition abolishes the production of large extracellular vesicles from Giardia intestinalis, affecting host-pathogen interactions by hindering adhesion to host cells. bioRxiv 586438. doi: 10.1101/586438

22. Chavanas S, Méchin MC, Nachat R, Adoue V, Coudane F, Serre G, et al. Peptidylarginine deiminases and deimination in biology and pathology: Relevance to skin homeostasis. Journal of Dermatological Science. 2006. pp. 63–72.

23. Senshu T, Kan S, Ogawa H, Manabe M, Asaga H. Preferential deimination of keratin K1 and filaggrin during the terminal differentiation of human epidermis. Biochem Biophys Res Commun. 1996;225: 712–719. doi: 10.1006/bbrc.1996.1240 8780679

24. Moscarello MA, Wood DD, Ackerley C, Boulias C. Myelin in multiple sclerosis is developmentally immature. J Clin Invest. 1994;94: 146–154. doi: 10.1172/JCI117300 7518827

25. Bhattacharya SK, Sinicrope B, Rayborn ME, Hollyfield JG, Bonilha VL. Age-related reduction in retinal deimination levels in the F344BN rat. Aging Cell. 2008;7: 441–444. doi: 10.1111/j.1474-9726.2008.00376.x 18248664

26. Cherrington BD, Zhang X, McElwee JL, Morency E, Anguish LJ, et al. (2012) Potential role for PAD2 in gene regulation in breast cancer cells. PLoS One 7: e41242. doi: 10.1371/journal.pone.0041242 22911765

27. Khandpur R, Carmona-Rivera C, Vivekanandan-Giri A, Gizinski A, Yalavarthi S, et al. (2013) NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis. Sci Transl Med 5: 178ra140.

28. Lamensa JW, Moscarello MA (1993) Deimination of human myelin basic protein by a peptidylarginine deiminase from bovine brain. J Neurochem 61: 987–996. doi: 10.1111/j.1471-4159.1993.tb03612.x 7689646

29. Mastronardi FG, Wood DD, Mei J, Raijmakers R, Tseveleki V, et al. (2006) Increased citrullination of histone H3 in multiple sclerosis brain and animal models of demyelination: a role for tumor necrosis factor-induced peptidylarginine deiminase 4 translocation. J Neurosci 26: 11387–11396. doi: 10.1523/JNEUROSCI.3349-06.2006 17079667

30. Acharya NK, Nagele EP, Han M, Coretti NJ, DeMarshall C, et al. (2012) Neuronal PAD4 expression and protein citrullination: possible role in production of autoantibodies associated with neurodegenerative disease. J Autoimmun 38: 369–380. doi: 10.1016/j.jaut.2012.03.004 22560840

31. Ishigami A, Ohsawa T, Hiratsuka M, Taguchi H, Kobayashi S, et al. (2005) Abnormal accumulation of citrullinated proteins catalyzed by peptidylarginine deiminase in hippocampal extracts from patients with Alzheimer's disease. J Neurosci Res 80: 120–128. doi: 10.1002/jnr.20431 15704193

32. Choi EK, Jang B, Ishigami A, Maruyama N, Carp RI, Kim YS. Deimination in prion diseases. Protein Deimination in Human Health and Disease. 2014. pp. 219–235.

33. Jang B, Jeon YC, Shin HY, Lee YJ, Kim H, Kondo Y, et al. Myelin Basic Protein Citrullination, a Hallmark of Central Nervous System Demyelination, Assessed by Novel Monoclonal Antibodies in Prion Diseases. Mol Neurobiol. 2018;55: 3172–3184. doi: 10.1007/s12035-017-0560-0 28470584

34. Musse AA, Zhen L, Ackerley CA, Bienzle D, Lei H, Poma R, et al. Peptidylarginine deiminase 2 (PAD2) overexpression in transgenic mice leads to myelin loss in the central nervous system. DMM Dis Model Mech. 2008;1: 229–240. doi: 10.1242/dmm.000729 19093029

35. Ding D, Enriquez-Algeciras M, Valdivia AO, Torres J, Pole C, Thompson JW, et al. The Role of Deimination in Regenerative Reprogramming of Neurons. Mol Neurobiol. 2019;56: 2618–2639. doi: 10.1007/s12035-018-1262-y 30051351

36. McElwee JL, Mohanan S, Horibata S, Sams KL, Anguish LJ, McLean D, et al. PAD2 overexpression in transgenic mice promotes spontaneous skin neoplasia. Cancer Res. 2014;74: 6306–6317. doi: 10.1158/0008-5472.CAN-14-0749 25213324

37. Mohanan S, Horibata S, Anguish LJ, et al (2017) PAD2 overexpression in transgenic mice augments malignancy and tumor-associated inflammation in chemically initiated skin tumors. Cell Tissue Res 370:275–283. doi: 10.1007/s00441-017-2669-x 28766045

38. Iijima K, Liu H-P, Chiang A-S, Hearn SA, Konsolaki M, et al. (2004) Dissecting the pathological effects of human Aβ40 and Aβ42 in Drosophila: A potential model for Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America 101: 6623–6628. doi: 10.1073/pnas.0400895101 15069204

39. Finelli A, Kelkar A, Song H-J, Yang H, Konsolaki M (2004) A model for studying Alzheimer's Aβ42-induced toxicity in Drosophila melanogaster. Molecular and Cellular Neuroscience 26: 365–375. doi: 10.1016/j.mcn.2004.03.001 15234342

40. Deleault NR, Dolph PJ, Feany MB, Cook ME, Nishina K, et al. (2003) Post-transcriptional suppression of pathogenic prion protein expression in Drosophila neurons. J Neurochem 85: 1614–1623. doi: 10.1046/j.1471-4159.2003.01819.x 12787080

41. Gavin BA, Dolph MJ, Deleault NR, Geoghegan JC, Khurana V, et al. (2006) Accelerated accumulation of misfolded prion protein and spongiform degeneration in a Drosophila model of Gerstmann-Straussler-Scheinker syndrome. J Neurosci 26: 12408–12414. doi: 10.1523/JNEUROSCI.3372-06.2006 17135402

42. Rubin GM, Spradling AC (1982) Genetic transformation of Drosophila with transposable element vectors. Science 218: 348–353. doi: 10.1126/science.6289436 6289436

43. Brand AH, Perrimon N (1993) Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118: 401–415. 8223268

44. Ja WW, Carvalho GB, Zid BM, Mak EM, Brummel T, et al. (2009) Water- and nutrient-dependent effects of dietary restriction on Drosophila lifespan. Proc Natl Acad Sci U S A 106: 18633–18637. doi: 10.1073/pnas.0908016106 19841272

45. Klose MK, Atwood HL, Robertson RM (2008) Hyperthermic preconditioning of presynaptic calcium regulation in Drosophila. J Neurophysiol 99: 2420–2430. doi: 10.1152/jn.01251.2007 18272873

46. Luo Y, Arita K, Bhatia M, Knuckley B, Lee YH, et al. (2006) Inhibitors and inactivators of protein arginine deiminase 4: functional and structural characterization. Biochemistry 45: 11727–11736. doi: 10.1021/bi061180d 17002273

47. Liu YL, Chiang YH, Liu GY, Hung HC (2011) Functional role of dimerization of human peptidylarginine deiminase 4 (PAD4). PLoS One 6: e21314. doi: 10.1371/journal.pone.0021314 21731701

48. Kearney PL, Bhatia M, Jones NG, Yuan L, Glascock MC, et al. (2005) Kinetic characterization of protein arginine deiminase 4: a transcriptional corepressor implicated in the onset and progression of rheumatoid arthritis. Biochemistry 44: 10570–10582. doi: 10.1021/bi050292m 16060666

49. Slade DJ, Fang P, Dreyton CJ, Zhang Y, Fuhrmann J, et al. (2015) Protein arginine deiminase 2 binds calcium in an ordered fashion: implications for inhibitor design. ACS Chem Biol 10: 1043–1053. doi: 10.1021/cb500933j 25621824

50. Darrah E, Giles JT, Ols ML, Bull HG, Andrade F, et al. (2013) Erosive rheumatoid arthritis is associated with antibodies that activate PAD4 by increasing calcium sensitivity. Sci Transl Med 5: 186ra165.

51. Jang B, Ishigami A, Maruyama N, Carp RI, Kim YS, et al. (2013) Peptidylarginine deiminase and protein citrullination in prion diseases: strong evidence of neurodegeneration. Prion 7: 42–46. doi: 10.4161/pri.22380 23022892

52. Jang B, Jin JK, Jeon YC, Cho HJ, Ishigami A, et al. (2010) Involvement of peptidylarginine deiminase-mediated post-translational citrullination in pathogenesis of sporadic Creutzfeldt-Jakob disease. Acta Neuropathol 119: 199–210. doi: 10.1007/s00401-009-0625-x 20013286

53. Macleod GT, Hegström-Wojtowicz M, Charlton MP, Atwood HL (2002) Fast Calcium Signals in Drosophila Motor Neuron Terminals. Journal of Neurophysiology 88: 2659–2663. doi: 10.1152/jn.00515.2002 12424301

54. Coudane F, Mechin MC, Huchenq A, Henry J, Nachat R, et al. (2011) Deimination and expression of peptidylarginine deiminases during cutaneous wound healing in mice. Eur J Dermatol 21: 376–384. doi: 10.1684/ejd.2011.1394 21697043

55. Gyorgy B, Toth E, Tarcsa E, Falus A, Buzas EI (2006) Citrullination: a posttranslational modification in health and disease. Int J Biochem Cell Biol 38: 1662–1677. doi: 10.1016/j.biocel.2006.03.008 16730216

56. Jones JE, Causey CP, Knuckley B, Slack-Noyes JL, Thompson PR (2009) Protein arginine deiminase 4 (PAD4): Current understanding and future therapeutic potential. Curr Opin Drug Discov Devel 12: 616–627. 19736621

In vivo expression of peptidylarginine deiminase in Drosophila melanogaster

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