ROS regulation of RAS and vulva development in Caenorhabditis elegans


Autoři: Maximilian Kramer-Drauberg aff001;  Ju-Ling Liu aff001;  David Desjardins aff001;  Ying Wang aff001;  Robyn Branicky aff001;  Siegfried Hekimi aff001
Působiště autorů: Department of Biology, McGill University, Montréal, Québec, Canada aff001
Vyšlo v časopise: ROS regulation of RAS and vulva development in Caenorhabditis elegans. PLoS Genet 16(6): e32767. doi:10.1371/journal.pgen.1008838
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008838

Souhrn

Reactive oxygen species (ROS) are signalling molecules whose study in intact organisms has been hampered by their potential toxicity. This has prevented a full understanding of their role in organismal processes such as development, aging and disease. In Caenorhabditis elegans, the development of the vulva is regulated by a signalling cascade that includes LET-60ras (homologue of mammalian Ras), MPK-1 (ERK1/2) and LIN-1 (an ETS transcription factor). We show that both mitochondrial and cytoplasmic ROS act on a gain-of-function (gf) mutant of the LET-60ras protein through a redox-sensitive cysteine (C118) previously identified in mammals. We show that the prooxidant paraquat as well as isp-1, nuo-6 and sod-2 mutants, which increase mitochondrial ROS, inhibit the activity of LET-60rasgf on vulval development. In contrast, the antioxidant NAC and loss of sod-1, both of which decrease cytoplasmic H202, enhance the activity of LET-60rasgf. CRISPR replacement of C118 with a non-oxidizable serine (C118S) stimulates LET-60rasgf activity, whereas replacement of C118 with aspartate (C118D), which mimics a strongly oxidised cysteine, inhibits LET-60rasgf. These data strongly suggest that C118 is oxidized by cytoplasmic H202 generated from dismutation of mitochondrial and/or cytoplasmic superoxide, and that this oxidation inhibits LET-60ras. This contrasts with results in cultured mammalian cells where it is mostly nitric oxide, which is not found in worms, that oxidizes C118 and activates Ras. Interestingly, PQ, NAC and the C118S mutation do not act on the phosphorylation of MPK-1, suggesting that oxidation of LET-60ras acts on an as yet uncharacterized MPK-1-independent pathway. We also show that elevated cytoplasmic superoxide promotes vulva formation independently of C118 of LET-60ras and downstream of LIN-1. Finally, we uncover a role for the NADPH oxidases (BLI-3 and DUOX-2) and their redox-sensitive activator CED-10rac in stimulating vulva development. Thus, there are at least three genetically separable pathways by which ROS regulates vulval development.

Klíčová slova:

Caenorhabditis elegans – Cysteine – Hydrogen peroxide – Mitochondria – Oxidation – Superoxide dismutase – Superoxides – Vulva


Zdroje

1. Holmstrom KM, Finkel T. Cellular mechanisms and physiological consequences of redox-dependent signalling. Nat Rev Mol Cell Biol. 2014;15(6):411–21. doi: 10.1038/nrm3801 24854789.

2. Sena LA, Chandel NS. Physiological roles of mitochondrial reactive oxygen species. Mol Cell. 2012;48(2):158–67. doi: 10.1016/j.molcel.2012.09.025 23102266; PubMed Central PMCID: PMC3484374.

3. Putker M, Madl T, Vos HR, de Ruiter H, Visscher M, van den Berg MC, et al. Redox-dependent control of FOXO/DAF-16 by transportin-1. Mol Cell. 2013;49(4):730–42. doi: 10.1016/j.molcel.2012.12.014 23333309.

4. Shibata Y, Branicky R, Landaverde IO, Hekimi S. Redox regulation of germline and vulval development in Caenorhabditis elegans. Science. 2003;302(5651):1779–82. doi: 10.1126/science.1087167 14657502.

5. Hourihan JM, Moronetti Mazzeo LE, Fernandez-Cardenas LP, Blackwell TK. Cysteine Sulfenylation Directs IRE-1 to Activate the SKN-1/Nrf2 Antioxidant Response. Mol Cell. 2016;63(4):553–66. doi: 10.1016/j.molcel.2016.07.019 27540856; PubMed Central PMCID: PMC4996358.

6. Xu S, Chisholm AD. C. elegans epidermal wounding induces a mitochondrial ROS burst that promotes wound repair. Dev Cell. 2014;31(1):48–60. doi: 10.1016/j.devcel.2014.08.002 25313960; PubMed Central PMCID: PMC4197410.

7. Ewald CY, Hourihan JM, Bland MS, Obieglo C, Katic I, Moronetti Mazzeo LE, et al. NADPH oxidase-mediated redox signaling promotes oxidative stress resistance and longevity through memo-1 in C. elegans. Elife. 2017;6. doi: 10.7554/eLife.19493 28085666; PubMed Central PMCID: PMC5235354.

8. Schmeisser S, Priebe S, Groth M, Monajembashi S, Hemmerich P, Guthke R, et al. Neuronal ROS signaling rather than AMPK/sirtuin-mediated energy sensing links dietary restriction to lifespan extension. Mol Metab. 2013;2(2):92–102. doi: 10.1016/j.molmet.2013.02.002 24199155; PubMed Central PMCID: PMC3817383.

9. Murphy MP. How mitochondria produce reactive oxygen species. Biochem J. 2009;417(1):1–13. doi: 10.1042/BJ20081386 19061483; PubMed Central PMCID: PMC2605959.

10. Kundu TK, Velayutham M, Zweier JL. Aldehyde oxidase functions as a superoxide generating NADH oxidase: an important redox regulated pathway of cellular oxygen radical formation. Biochemistry. 2012;51(13):2930–9. doi: 10.1021/bi3000879 22404107; PubMed Central PMCID: PMC3954720.

11. Zangar RC, Davydov DR, Verma S. Mechanisms that regulate production of reactive oxygen species by cytochrome P450. Toxicol Appl Pharmacol. 2004;199(3):316–31. doi: 10.1016/j.taap.2004.01.018 15364547.

12. Bedard K, Krause KH. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev. 2007;87(1):245–313. doi: 10.1152/physrev.00044.2005 17237347.

13. Fridovich I. Superoxide anion radical (O2-.), superoxide dismutases, and related matters. J Biol Chem. 1997;272(30):18515–7. doi: 10.1074/jbc.272.30.18515 9228011.

14. Kelley EE, Khoo NK, Hundley NJ, Malik UZ, Freeman BA, Tarpey MM. Hydrogen peroxide is the major oxidant product of xanthine oxidase. Free Radic Biol Med. 2010;48(4):493–8. doi: 10.1016/j.freeradbiomed.2009.11.012 19941951; PubMed Central PMCID: PMC2848256.

15. Edmondson DE. Hydrogen peroxide produced by mitochondrial monoamine oxidase catalysis: biological implications. Curr Pharm Des. 2014;20(2):155–60. doi: 10.2174/13816128113190990406 23701542.

16. Lambeth JD, Neish AS. Nox enzymes and new thinking on reactive oxygen: a double-edged sword revisited. Annu Rev Pathol. 2014;9:119–45. doi: 10.1146/annurev-pathol-012513-104651 24050626.

17. Zamocky M, Koller F. Understanding the structure and function of catalases: clues from molecular evolution and in vitro mutagenesis. Prog Biophys Mol Biol. 1999;72(1):19–66. doi: 10.1016/s0079-6107(98)00058-3 10446501.

18. Toppo S, Flohe L, Ursini F, Vanin S, Maiorino M. Catalytic mechanisms and specificities of glutathione peroxidases: variations of a basic scheme. Biochim Biophys Acta. 2009;1790(11):1486–500. doi: 10.1016/j.bbagen.2009.04.007 19376195.

19. Hanschmann EM, Godoy JR, Berndt C, Hudemann C, Lillig CH. Thioredoxins, glutaredoxins, and peroxiredoxins—molecular mechanisms and health significance: from cofactors to antioxidants to redox signaling. Antioxid Redox Signal. 2013;19(13):1539–605. doi: 10.1089/ars.2012.4599 23397885; PubMed Central PMCID: PMC3797455.

20. Wang Y, Branicky R, Noe A, Hekimi S. Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling. J Cell Biol. 2018;217(6):1915–28. doi: 10.1083/jcb.201708007 29669742; PubMed Central PMCID: PMC5987716.

21. Meitzler JL, Brandman R, Ortiz de Montellano PR. Perturbed heme binding is responsible for the blistering phenotype associated with mutations in the Caenorhabditis elegans dual oxidase 1 (DUOX1) peroxidase domain. J Biol Chem. 2010;285(52):40991–1000. doi: 10.1074/jbc.M110.170902 20947510; PubMed Central PMCID: PMC3003398.

22. Thein MC, Winter AD, Stepek G, McCormack G, Stapleton G, Johnstone IL, et al. Combined extracellular matrix cross-linking activity of the peroxidase MLT-7 and the dual oxidase BLI-3 is critical for post-embryonic viability in Caenorhabditis elegans. J Biol Chem. 2009;284(26):17549–63. doi: 10.1074/jbc.M900831200 19406744; PubMed Central PMCID: PMC2719394.

23. Edens WA, Sharling L, Cheng G, Shapira R, Kinkade JM, Lee T, et al. Tyrosine cross-linking of extracellular matrix is catalyzed by Duox, a multidomain oxidase/peroxidase with homology to the phagocyte oxidase subunit gp91phox. J Cell Biol. 2001;154(4):879–91. doi: 10.1083/jcb.200103132 11514595; PubMed Central PMCID: PMC2196470.

24. McCallum KC, Garsin DA. The Role of Reactive Oxygen Species in Modulating the Caenorhabditis elegans Immune Response. PLoS Pathog. 2016;12(11):e1005923. doi: 10.1371/journal.ppat.1005923 27832190; PubMed Central PMCID: PMC5104326.

25. Ewald CY. Redox Signaling of NADPH Oxidases Regulates Oxidative Stress Responses, Immunity and Aging. Antioxidants (Basel). 2018;7(10). doi: 10.3390/antiox7100130 30274229; PubMed Central PMCID: PMC6210377.

26. Guyton KZ, Liu Y, Gorospe M, Xu Q, Holbrook NJ. Activation of mitogen-activated protein kinase by H2O2. Role in cell survival following oxidant injury. J Biol Chem. 1996;271(8):4138–42. doi: 10.1074/jbc.271.8.4138 8626753.

27. Lander HM, Hajjar DP, Hempstead BL, Mirza UA, Chait BT, Campbell S, et al. A molecular redox switch on p21(ras). Structural basis for the nitric oxide-p21(ras) interaction. J Biol Chem. 1997;272(7):4323–6. doi: 10.1074/jbc.272.7.4323 9020151.

28. Liu Y, Zhi D, Li M, Liu D, Wang X, Wu Z, et al. Shengmai Formula suppressed over-activated Ras/MAPK pathway in C. elegans by opening mitochondrial permeability transition pore via regulating cyclophilin D. Sci Rep. 2016;6:38934. doi: 10.1038/srep38934 27982058; PubMed Central PMCID: PMC5159904.

29. Heo J, Campbell SL. Superoxide anion radical modulates the activity of Ras and Ras-related GTPases by a radical-based mechanism similar to that of nitric oxide. J Biol Chem. 2005;280(13):12438–45. doi: 10.1074/jbc.M414282200 15684418.

30. Heo J, Prutzman KC, Mocanu V, Campbell SL. Mechanism of free radical nitric oxide-mediated Ras guanine nucleotide dissociation. J Mol Biol. 2005;346(5):1423–40. doi: 10.1016/j.jmb.2004.12.050 15713491.

31. Heo J, Campbell SL. Ras regulation by reactive oxygen and nitrogen species. Biochemistry. 2006;45(7):2200–10. doi: 10.1021/bi051872m 16475808.

32. Heo J, Campbell SL. Mechanism of p21Ras S-nitrosylation and kinetics of nitric oxide-mediated guanine nucleotide exchange. Biochemistry. 2004;43(8):2314–22. doi: 10.1021/bi035275g 14979728.

33. Mott HR, Carpenter JW, Campbell SL. Structural and functional analysis of a mutant Ras protein that is insensitive to nitric oxide activation. Biochemistry. 1997;36(12):3640–4. doi: 10.1021/bi962790o 9132016.

34. Huang L, Counter CM. Reduced HRAS G12V-Driven Tumorigenesis of Cell Lines Expressing KRAS C118S. PLoS One. 2015;10(4):e0123918. doi: 10.1371/journal.pone.0123918 25902334; PubMed Central PMCID: PMC4406447.

35. Ibiza S, Perez-Rodriguez A, Ortega A, Martinez-Ruiz A, Barreiro O, Garcia-Dominguez CA, et al. Endothelial nitric oxide synthase regulates N-Ras activation on the Golgi complex of antigen-stimulated T cells. Proc Natl Acad Sci U S A. 2008;105(30):10507–12. doi: 10.1073/pnas.0711062105 18641128; PubMed Central PMCID: PMC2492470.

36. Mallis RJ, Buss JE, Thomas JA. Oxidative modification of H-ras: S-thiolation and S-nitrosylation of reactive cysteines. Biochem J. 2001;355(Pt 1):145–53. doi: 10.1042/0264-6021:3550145 11256959; PubMed Central PMCID: PMC1221722.

37. Huang L, Carney J, Cardona DM, Counter CM. Decreased tumorigenesis in mice with a Kras point mutation at C118. Nat Commun. 2014;5:5410. doi: 10.1038/ncomms6410 25394415; PubMed Central PMCID: PMC4234187.

38. Hobbs GA, Mitchell LE, Arrington ME, Gunawardena HP, DeCristo MJ, Loeser RF, et al. Redox regulation of Rac1 by thiol oxidation. Free Radic Biol Med. 2015;79:237–50. doi: 10.1016/j.freeradbiomed.2014.09.027 25289457; PubMed Central PMCID: PMC4708892.

39. Heo J, Raines KW, Mocanu V, Campbell SL. Redox regulation of RhoA. Biochemistry. 2006;45(48):14481–9. doi: 10.1021/bi0610101 17128987.

40. Permyakov SE, Zernii EY, Knyazeva EL, Denesyuk AI, Nazipova AA, Kolpakova TV, et al. Oxidation mimicking substitution of conservative cysteine in recoverin suppresses its membrane association. Amino Acids. 2012;42(4):1435–42. doi: 10.1007/s00726-011-0843-0 21344177.

41. Sternberg PW. Vulval development In: Community TCeR, editor. WormBook2005.

42. Sundaram MV. Canonical RTK-Ras-ERK signaling and related alternative pathways. WormBook. 2013:1–38. doi: 10.1895/wormbook.1.80.2 23908058; PubMed Central PMCID: PMC3885983.

43. Reiner DJ, Lundquist EA. Small GTPases. In: Community TCeR, editor. WormBook: WormBook.

44. Han M, Sternberg PW. let-60, a gene that specifies cell fates during C. elegans vulval induction, encodes a ras protein. Cell. 1990;63(5):921–31. doi: 10.1016/0092-8674(90)90495-z 2257629.

45. Smith MJ, Neel BG, Ikura M. NMR-based functional profiling of RASopathies and oncogenic RAS mutations. Proc Natl Acad Sci U S A. 2013;110(12):4574–9. doi: 10.1073/pnas.1218173110 23487764; PubMed Central PMCID: PMC3607025.

46. Lu S, Jang H, Nussinov R, Zhang J. The Structural Basis of Oncogenic Mutations G12, G13 and Q61 in Small GTPase K-Ras4B. Sci Rep. 2016;6:21949. doi: 10.1038/srep21949 26902995; PubMed Central PMCID: PMC4763299.

47. Lackner MR, Kim SK. Genetic analysis of the Caenorhabditis elegans MAP kinase gene mpk-1. Genetics. 1998;150(1):103–17. 9725833; PubMed Central PMCID: PMC1460334.

48. Beitel GJ, Tuck S, Greenwald I, Horvitz HR. The Caenorhabditis elegans gene lin-1 encodes an ETS-domain protein and defines a branch of the vulval induction pathway. Genes Dev. 1995;9(24):3149–62. doi: 10.1101/gad.9.24.3149 8543158.

49. Reczek CR, Birsoy K, Kong H, Martinez-Reyes I, Wang T, Gao P, et al. A CRISPR screen identifies a pathway required for paraquat-induced cell death. Nat Chem Biol. 2017;13(12):1274–9. doi: 10.1038/nchembio.2499 29058724; PubMed Central PMCID: PMC5698099.

50. Cocheme HM, Murphy MP. Complex I is the major site of mitochondrial superoxide production by paraquat. J Biol Chem. 2008;283(4):1786–98. doi: 10.1074/jbc.M708597200 18039652.

51. Castello PR, Drechsel DA, Patel M. Mitochondria are a major source of paraquat-induced reactive oxygen species production in the brain. J Biol Chem. 2007;282(19):14186–93. doi: 10.1074/jbc.M700827200 17389593; PubMed Central PMCID: PMC3088512.

52. Yang W, Hekimi S. A mitochondrial superoxide signal triggers increased longevity in Caenorhabditis elegans. PLoS Biol. 2010;8(12):e1000556. doi: 10.1371/journal.pbio.1000556 21151885; PubMed Central PMCID: PMC2998438.

53. Yang W, Li J, Hekimi S. A Measurable increase in oxidative damage due to reduction in superoxide detoxification fails to shorten the life span of long-lived mitochondrial mutants of Caenorhabditis elegans. Genetics. 2007;177(4):2063–74. doi: 10.1534/genetics.107.080788 18073424; PubMed Central PMCID: PMC2219504.

54. Aruoma OI, Halliwell B, Hoey BM, Butler J. The antioxidant action of N-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid. Free Radic Biol Med. 1989;6(6):593–7. doi: 10.1016/0891-5849(89)90066-x 2546864.

55. Desjardins D, Cacho-Valadez B, Liu JL, Wang Y, Yee C, Bernard K, et al. Antioxidants reveal an inverted U-shaped dose-response relationship between reactive oxygen species levels and the rate of aging in Caenorhabditis elegans. Aging Cell. 2017;16(1):104–12. Epub 2016/09/30. doi: 10.1111/acel.12528 27683245; PubMed Central PMCID: PMC5242296.

56. Eisenmann DM, Kim SK. Mechanism of activation of the Caenorhabditis elegans ras homologue let-60 by a novel, temperature-sensitive, gain-of-function mutation. Genetics. 1997;146(2):553–65. Epub 1997/06/01. 9178006; PubMed Central PMCID: PMC1207997.

57. Morton DB, Hudson ML, Waters E, O'Shea M. Soluble guanylyl cyclases in Caenorhabditis elegans: NO is not the answer. Curr Biol. 1999;9(15):R546–7. doi: 10.1016/s0960-9822(99)80349-2 10469574.

58. Paix A, Folkmann A, Rasoloson D, Seydoux G. High Efficiency, Homology-Directed Genome Editing in Caenorhabditis elegans Using CRISPR-Cas9 Ribonucleoprotein Complexes. Genetics. 2015;201(1):47–54. doi: 10.1534/genetics.115.179382 26187122; PubMed Central PMCID: PMC4566275.

59. Lo Conte M, Carroll KS. The redox biochemistry of protein sulfenylation and sulfinylation. J Biol Chem. 2013;288(37):26480–8. doi: 10.1074/jbc.R113.467738 23861405; PubMed Central PMCID: PMC3772195.

60. Romagnolo B, Jiang M, Kiraly M, Breton C, Begley R, Wang J, et al. Downstream targets of let-60 Ras in Caenorhabditis elegans. Dev Biol. 2002;247(1):127–36. doi: 10.1006/dbio.2002.0692 12074557.

61. Ohmachi M, Rocheleau CE, Church D, Lambie E, Schedl T, Sundaram MV. C. elegans ksr-1 and ksr-2 have both unique and redundant functions and are required for MPK-1 ERK phosphorylation. Curr Biol. 2002;12(5):427–33. doi: 10.1016/s0960-9822(02)00690-5 11882296.

62. Sundaram M, Han M. The C. elegans ksr-1 gene encodes a novel Raf-related kinase involved in Ras-mediated signal transduction. Cell. 1995;83(6):889–901. Epub 1995/12/15. doi: 10.1016/0092-8674(95)90205-8 8521513.

63. Doonan R, McElwee JJ, Matthijssens F, Walker GA, Houthoofd K, Back P, et al. Against the oxidative damage theory of aging: superoxide dismutases protect against oxidative stress but have little or no effect on life span in Caenorhabditis elegans. Genes Dev. 2008;22(23):3236–41. doi: 10.1101/gad.504808 19056880; PubMed Central PMCID: PMC2600764.

64. Yanase S, Onodera A, Tedesco P, Johnson TE, Ishii N. SOD-1 deletions in Caenorhabditis elegans alter the localization of intracellular reactive oxygen species and show molecular compensation. J Gerontol A Biol Sci Med Sci. 2009;64(5):530–9. doi: 10.1093/gerona/glp020 19282511.

65. Jezek J, Cooper KF, Strich R. Reactive Oxygen Species and Mitochondrial Dynamics: The Yin and Yang of Mitochondrial Dysfunction and Cancer Progression. Antioxidants (Basel). 2018;7(1). doi: 10.3390/antiox7010013 29337889; PubMed Central PMCID: PMC5789323.

66. Lee J, Giordano S, Zhang J. Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling. Biochem J. 2012;441(2):523–40. doi: 10.1042/BJ20111451 22187934; PubMed Central PMCID: PMC3258656.

67. Chandel NS. Mitochondria as signaling organelles. BMC Biol. 2014;12:34. doi: 10.1186/1741-7007-12-34 24884669; PubMed Central PMCID: PMC4035690.

68. Finkel T. Signal transduction by reactive oxygen species. J Cell Biol. 2011;194(1):7–15. doi: 10.1083/jcb.201102095 21746850; PubMed Central PMCID: PMC3135394.

69. Shadel GS, Horvath TL. Mitochondrial ROS signaling in organismal homeostasis. Cell. 2015;163(3):560–9. doi: 10.1016/j.cell.2015.10.001 26496603; PubMed Central PMCID: PMC4634671.

70. Van Raamsdonk JM, Hekimi S. Reactive Oxygen Species and Aging in Caenorhabditis elegans: Causal or Casual Relationship? Antioxid Redox Signal. 2010;13(12):1911–53. doi: 10.1089/ars.2010.3215 20568954.

71. Van Raamsdonk JM, Hekimi S. Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in Caenorhabditis elegans. PLoS Genet. 2009;5(2):e1000361. doi: 10.1371/journal.pgen.1000361 19197346; PubMed Central PMCID: PMC2628729.

72. Feng J, Bussiere F, Hekimi S. Mitochondrial electron transport is a key determinant of life span in Caenorhabditis elegans. Dev Cell. 2001;1(5):633–44. doi: 10.1016/s1534-5807(01)00071-5 11709184.

73. Yang W, Hekimi S. Two modes of mitochondrial dysfunction lead independently to lifespan extension in Caenorhabditis elegans. Aging Cell. 2010;9(3):433–47. doi: 10.1111/j.1474-9726.2010.00571.x 20346072.

74. Han D, Antunes F, Canali R, Rettori D, Cadenas E. Voltage-dependent anion channels control the release of the superoxide anion from mitochondria to cytosol. J Biol Chem. 2003;278(8):5557–63. doi: 10.1074/jbc.M210269200 12482755.

75. Lustgarten MS, Bhattacharya A, Muller FL, Jang YC, Shimizu T, Shirasawa T, et al. Complex I generated, mitochondrial matrix-directed superoxide is released from the mitochondria through voltage dependent anion channels. Biochem Biophys Res Commun. 2012;422(3):515–21. doi: 10.1016/j.bbrc.2012.05.055 22613204; PubMed Central PMCID: PMC3400138.

76. Bienert GP, Moller AL, Kristiansen KA, Schulz A, Moller IM, Schjoerring JK, et al. Specific aquaporins facilitate the diffusion of hydrogen peroxide across membranes. J Biol Chem. 2007;282(2):1183–92. doi: 10.1074/jbc.M603761200 17105724.

77. van der Hoeven R, Cruz MR, Chavez V, Garsin DA. Localization of the Dual Oxidase BLI-3 and Characterization of Its NADPH Oxidase Domain during Infection of Caenorhabditis elegans. PLoS One. 2015;10(4):e0124091. Epub 2015/04/25. doi: 10.1371/journal.pone.0124091 25909649; PubMed Central PMCID: PMC4409361.

78. Brandes RP, Weissmann N, Schroder K. Nox family NADPH oxidases: Molecular mechanisms of activation. Free Radic Biol Med. 2014;76:208–26. doi: 10.1016/j.freeradbiomed.2014.07.046 25157786.

79. Reiner DJ, Lundquist EA. Small GTPases. WormBook. 2018;2018:1–65. Epub 2016/05/25. doi: 10.1895/wormbook.1.67.2 27218782; PubMed Central PMCID: PMC6369420.

80. Kishore RS, Sundaram MV. ced-10 Rac and mig-2 function redundantly and act with unc-73 trio to control the orientation of vulval cell divisions and migrations in Caenorhabditis elegans. Dev Biol. 2002;241(2):339–48. Epub 2002/01/11. doi: 10.1006/dbio.2001.0513 11784116.

81. Hanzen S, Vielfort K, Yang J, Roger F, Andersson V, Zamarbide-Fores S, et al. Lifespan Control by Redox-Dependent Recruitment of Chaperones to Misfolded Proteins. Cell. 2016;166(1):140–51. doi: 10.1016/j.cell.2016.05.006 27264606.

82. Meyer AJ, Dick TP. Fluorescent protein-based redox probes. Antioxid Redox Signal. 2010;13(5):621–50. doi: 10.1089/ars.2009.2948 20088706.

83. Denu JM, Tanner KG. Specific and reversible inactivation of protein tyrosine phosphatases by hydrogen peroxide: evidence for a sulfenic acid intermediate and implications for redox regulation. Biochemistry. 1998;37(16):5633–42. Epub 1998/05/16. doi: 10.1021/bi973035t 9548949.

84. Lackner MR, Kornfeld K, Miller LM, Horvitz HR, Kim SK. A MAP kinase homolog, mpk-1, is involved in ras-mediated induction of vulval cell fates in Caenorhabditis elegans. Genes Dev. 1994;8(2):160–73. doi: 10.1101/gad.8.2.160 8299936.

85. Zand TP, Reiner DJ, Der CJ. Ras effector switching promotes divergent cell fates in C. elegans vulval patterning. Dev Cell. 2011;20(1):84–96. Epub 2011/01/18. doi: 10.1016/j.devcel.2010.12.004 21238927; PubMed Central PMCID: PMC3028984.

Štítky
Genetika Reprodukční medicína

Článek vyšel v časopise

PLOS Genetics


2020 Číslo 6

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…


Kurzy Doporučená témata Časopisy
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

VIRTUÁLNÍ ČEKÁRNA ČR Jste praktický lékař nebo pediatr? Zapojte se! Jste praktik nebo pediatr? Zapojte se!

×