A Shift to Organismal Stress Resistance in Programmed Cell Death Mutants

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Animals have many ways of protecting themselves against stress; for example, they can induce animal-wide, stress-protective pathways and they can kill damaged cells via apoptosis. We have discovered an unexpected regulatory relationship between these two types of stress responses. We find that C. elegans mutations blocking the normal course of programmed cell death and clearance confer animal-wide resistance to a specific set of environmental stressors; namely, ER, heat and osmotic stress. Remarkably, this pattern of stress resistance is induced by mutations that affect cell death in different ways, including ced-3 (cell death defective) mutations, which block programmed cell death, ced-1 and ced-2 mutations, which prevent the engulfment of dying cells, and progranulin (pgrn-1) mutations, which accelerate the clearance of apoptotic cells. Stress resistance conferred by ced and pgrn-1 mutations is not additive and these mutants share altered patterns of gene expression, suggesting that they may act within the same pathway to achieve stress resistance. Together, our findings demonstrate that programmed cell death effectors influence the degree to which C. elegans tolerates environmental stress. While the mechanism is not entirely clear, it is intriguing that animals lacking the ability to efficiently and correctly remove dying cells should switch to a more global animal-wide system of stress resistance.

Vyšlo v časopise: A Shift to Organismal Stress Resistance in Programmed Cell Death Mutants. PLoS Genet 9(9): e32767. doi:10.1371/journal.pgen.1003714
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003714

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Zdroje

1. CypserJR, TedescoP, JohnsonTE (2006) Hormesis and aging in Caenorhabditis elegans. Exp Gerontol 41 : 935–939.

2. GartnerA, BoagPR, BlackwellTK (2008) Germline survival and apoptosis. WormBook 1–20.

3. BargmannCI (1993) Genetic and cellular analysis of behavior in C. elegans. Annu Rev Neurosci 16 : 47–71.

4. GoldenJW, RiddleDL (1982) A pheromone influences larval development in the nematode Caenorhabditis elegans. Science 218 : 578–580.

5. Hajdu-CroninYM, ChenWJ, SternbergPW (2004) The L-type cyclin CYL-1 and the heat-shock-factor HSF-1 are required for heat-shock-induced protein expression in Caenorhabditis elegans. Genetics 168 : 1937–1949.

6. AnJH, BlackwellTK (2003) SKN-1 links C. elegans mesendodermal specification to a conserved oxidative stress response. Genes Dev 17 : 1882–1893.

7. JiangH, GuoR, Powell-CoffmanJA (2001) The Caenorhabditis elegans hif-1 gene encodes a bHLH-PAS protein that is required for adaptation to hypoxia. Proc Natl Acad Sci U S A 98 : 7916–7921.

8. GartnerA, MilsteinS, AhmedS, HodgkinJ, HengartnerMO (2000) A conserved checkpoint pathway mediates DNA damage–induced apoptosis and cell cycle arrest in C. elegans. Mol Cell 5 : 435–443.

9. GumiennyTL, LambieE, HartwiegE, HorvitzHR, HengartnerMO (1999) Genetic control of programmed cell death in the Caenorhabditis elegans hermaphrodite germline. Development 126 : 1011–1022.

10. KerrJF, WyllieAH, CurrieAR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26 : 239–257.

11. HoeppnerDJ, HengartnerMO, SchnabelR (2001) Engulfment genes cooperate with ced-3 to promote cell death in Caenorhabditis elegans. Nature 412 : 202–206.

12. ReddienPW, CameronS, HorvitzHR (2001) Phagocytosis promotes programmed cell death in C. elegans. Nature 412 : 198–202.

13. ElliottMR, RavichandranKS (2010) Clearance of apoptotic cells: implications in health and disease. J Cell Biol 189 : 1059–1070.

14. SulstonJE, SchierenbergE, WhiteJG, ThomsonJN (1983) The embryonic cell lineage of the nematode Caenorhabditis elegans. Dev Biol 100 : 64–119.

15. EllisHM, HorvitzHR (1986) Genetic control of programmed cell death in the nematode C. elegans. Cell 44 : 817–829.

16. HengartnerMO, EllisRE, HorvitzHR (1992) Caenorhabditis elegans gene ced-9 protects cells from programmed cell death. Nature 356 : 494–499.

17. SpectorMS, DesnoyersS, HoeppnerDJ, HengartnerMO (1997) Interaction between the C. elegans cell-death regulators CED-9 and CED-4. Nature 385 : 653–656.

18. WuD, WallenHD, NunezG (1997) Interaction and regulation of subcellular localization of CED-4 by CED-9. Science 275 : 1126–1129.

19. ConradtB, HorvitzHR (1998) The C. elegans protein EGL-1 is required for programmed cell death and interacts with the Bcl-2-like protein CED-9. Cell 93 : 519–529.

20. YuanJY, HorvitzHR (1990) The Caenorhabditis elegans genes ced-3 and ced-4 act cell autonomously to cause programmed cell death. Dev Biol 138 : 33–41.

21. YuanJ, ShahamS, LedouxS, EllisHM, HorvitzHR (1993) The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme. Cell 75 : 641–652.

22. HedgecockEM, SulstonJE, ThomsonJN (1983) Mutations affecting programmed cell deaths in the nematode Caenorhabditis elegans. Science 220 : 1277–1279.

23. EllisRE, JacobsonDM, HorvitzHR (1991) Genes required for the engulfment of cell corpses during programmed cell death in Caenorhabditis elegans. Genetics 129 : 79–94.

24. ConradtB, XueD (2005) Programmed cell death. WormBook 1–13.

25. ZouW, LuQ, ZhaoD, LiW, MapesJ, et al. (2009) Caenorhabditis elegans myotubularin MTM-1 negatively regulates the engulfment of apoptotic cells. PLoS Genet 5: e1000679.

26. KaoAW, EisenhutRJ, Herl MartensL, NakamuraA, HuangA, et al. (2011) A neurodegenerative disease mutation that accelerates the clearance of apoptotic cells. Proc Natl Acad Sci U S A 108 : 4441–4446.

27. BakerM, MackenzieIR, Pickering-BrownSM, GassJ, RademakersR, et al. (2006) Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature 442 : 916–919.

28. CrutsM, Kumar-SinghS, Van BroeckhovenC (2006) Progranulin mutations in ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Curr Alzheimer Res 3 : 485–491.

29. SmithKR, DamianoJ, FranceschettiS, CarpenterS, CanafogliaL, et al. (2012) Strikingly different clinicopathological phenotypes determined by progranulin-mutation dosage. Am J Hum Genet 90 : 1102–1107.

30. BrouwersN, NuytemansK, van der ZeeJ, GijselinckI, EngelborghsS, et al. (2007) Alzheimer and Parkinson diagnoses in progranulin null mutation carriers in an extended founder family. Arch Neurol 64 : 1436–1446.

31. BrouwersN, SleegersK, EngelborghsS, Maurer-StrohS, GijselinckI, et al. (2008) Genetic variability in progranulin contributes to risk for clinically diagnosed Alzheimer disease. Neurology 71 : 656–664.

32. SleegersK, BrouwersN, Maurer-StrohS, van EsMA, Van DammeP, et al. (2008) Progranulin genetic variability contributes to amyotrophic lateral sclerosis. Neurology 71 : 253–259.

33. ViswanathanJ, MakinenP, HelisalmiS, HaapasaloA, SoininenH, et al. (2009) An association study between granulin gene polymorphisms and Alzheimer's disease in Finnish population. Am J Med Genet B Neuropsychiatr Genet 150B: 747–750.

34. LeeMJ, ChenTF, ChengTW, ChiuMJ (2011) rs5848 variant of progranulin gene is a risk of Alzheimer's disease in the Taiwanese population. Neurodegener Dis 8 : 216–220.

35. TangW, LuY, TianQY, ZhangY, GuoFJ, et al. (2011) The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science 332 : 478–484.

36. MatsubaraT, MitaA, MinamiK, HosookaT, KitazawaS, et al. (2012) PGRN is a key adipokine mediating high fat diet-induced insulin resistance and obesity through IL-6 in adipose tissue. Cell Metab 15 : 38–50.

37. HeZ, IsmailA, KriazhevL, SadvakassovaG, BatemanA (2002) Progranulin (PC-cell-derived growth factor/acrogranin) regulates invasion and cell survival. Cancer Res 62 : 5590–5596.

38. HoJC, IpYC, CheungST, LeeYT, ChanKF, et al. (2008) Granulin-epithelin precursor as a therapeutic target for hepatocellular carcinoma. Hepatology 47 : 1524–1532.

39. KamravaM, SimpkinsF, AlejandroE, MichenerC, MeltzerE, et al. (2005) Lysophosphatidic acid and endothelin-induced proliferation of ovarian cancer cell lines is mitigated by neutralization of granulin-epithelin precursor (GEP), a prosurvival factor for ovarian cancer. Oncogene 24 : 7084–7093.

40. MatsumuraN, MandaiM, MiyanishiM, FukuharaK, BabaT, et al. (2006) Oncogenic property of acrogranin in human uterine leiomyosarcoma: direct evidence of genetic contribution in in vivo tumorigenesis. Clin Cancer Res 12 : 1402–1411.

41. PanCX, KinchMS, KienerPA, LangermannS, SerreroG, et al. (2004) PC cell-derived growth factor expression in prostatic intraepithelial neoplasia and prostatic adenocarcinoma. Clin Cancer Res 10 : 1333–1337.

42. WangM, LiG, YinJ, LinT, ZhangJ (2011) Progranulin overexpression predicts overall survival in patients with glioblastoma. Med Oncol 29 ((4)): 2423–31.

43. TaoJ, JiF, WangF, LiuB, ZhuY (2011) Neuroprotective effects of progranulin in ischemic mice. Brain Res 1436 : 130–136.

44. XuJ, XilouriM, BrubanJ, ShioiJ, ShaoZ, et al. (2011) Extracellular progranulin protects cortical neurons from toxic insults by activating survival signaling. Neurobiol Aging 32 : 2326 e2325–2316.

45. HurwitzME, VanderzalmPJ, BloomL, GoldmanJ, GarrigaG, et al. (2009) Abl kinase inhibits the engulfment of apoptotic cells in Caenorhabditis elegans. PLoS Biol 7: e99.

46. NeukommLJ, FreiAP, CabelloJ, KinchenJM, Zaidel-BarR, et al. (2011) Loss of the RhoGAP SRGP-1 promotes the clearance of dead and injured cells in Caenorhabditis elegans. Nat Cell Biol 13 : 79–86.

47. NeukommLJ, NicotAS, KinchenJM, AlmendingerJ, PintoSM, et al. (2011) The phosphoinositide phosphatase MTM-1 regulates apoptotic cell corpse clearance through CED-5-CED-12 in C. elegans. Development 138 : 2003–2014.

48. OlsenA, VantipalliMC, LithgowGJ (2006) Lifespan extension of Caenorhabditis elegans following repeated mild hormetic heat treatments. Biogerontology 7 : 221–230.

49. UranoF, CalfonM, YonedaT, YunC, KiralyM, et al. (2002) A survival pathway for Caenorhabditis elegans with a blocked unfolded protein response. J Cell Biol 158 : 639–646.

50. ShahamS, ReddienPW, DaviesB, HorvitzHR (1999) Mutational analysis of the Caenorhabditis elegans cell-death gene ced-3. Genetics 153 : 1655–1671.

51. YangX, ChangHY, BaltimoreD (1998) Essential role of CED-4 oligomerization in CED-3 activation and apoptosis. Science 281 : 1355–1357.

52. deBakkerCD, HaneyLB, KinchenJM, GrimsleyC, LuM, et al. (2004) Phagocytosis of apoptotic cells is regulated by a UNC-73/TRIO-MIG-2/RhoG signaling module and armadillo repeats of CED-12/ELMO. Curr Biol 14 : 2208–2216.

53. SchmidtKL, Marcus-GueretN, AdeleyeA, WebberJ, BaillieD, et al. (2009) The cell migration molecule UNC-53/NAV2 is linked to the ARP2/3 complex by ABI-1. Development 136 : 563–574.

54. BlumES, AbrahamMC, YoshimuraS, LuY, ShahamS (2012) Control of nonapoptotic developmental cell death in Caenorhabditis elegans by a polyglutamine-repeat protein. Science 335 : 970–973.

55. AbrahamMC, LuY, ShahamS (2007) A morphologically conserved nonapoptotic program promotes linker cell death in Caenorhabditis elegans. Dev Cell 12 : 73–86.

56. BlumES, DriscollM, ShahamS (2008) Noncanonical cell death programs in the nematode Caenorhabditis elegans. Cell Death Differ 15 : 1124–1131.

57. OzcanL, TabasI (2012) Role of endoplasmic reticulum stress in metabolic disease and other disorders. Annu Rev Med 63 : 317–328.

58. RonD, WalterP (2007) Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 8 : 519–529.

59. ShenX, EllisRE, LeeK, LiuCY, YangK, et al. (2001) Complementary signaling pathways regulate the unfolded protein response and are required for C. elegans development. Cell 107 : 893–903.

60. Henis-KorenblitS, ZhangP, HansenM, McCormickM, LeeSJ, et al. (2010) Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A 107 : 9730–9735.

61. XuSQ, TangD, ChamberlainS, PronkG, MasiarzFR, et al. (1998) The granulin/epithelin precursor abrogates the requirement for the insulin-like growth factor 1 receptor for growth in vitro. J Biol Chem 273 : 20078–20083.

62. Zanocco-MaraniT, BatemanA, RomanoG, ValentinisB, HeZH, et al. (1999) Biological activities and signaling pathways of the granulin/epithelin precursor. Cancer Res 59 : 5331–5340.

63. KenyonC, ChangJ, GenschE, RudnerA, TabtiangR (1993) A C. elegans mutant that lives twice as long as wild type. Nature 366 : 461–464.

64. LithgowGJ, WhiteTM, MelovS, JohnsonTE (1995) Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress. Proc Natl Acad Sci U S A 92 : 7540–7544.

65. LinK, HsinH, LibinaN, KenyonC (2001) Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germline signaling. Nat Genet 28 : 139–145.

66. CurranSP, RuvkunG (2007) Lifespan regulation by evolutionarily conserved genes essential for viability. PLoS Genet 3: e56.

67. ShoreDE, CarrCE, RuvkunG (2012) Induction of cytoprotective pathways is central to the extension of lifespan conferred by multiple longevity pathways. PLoS Genet 8: e1002792.

68. InoueH, HisamotoN, AnJH, OliveiraRP, NishidaE, et al. (2005) The C. elegans p38 MAPK pathway regulates nuclear localization of the transcription factor SKN-1 in oxidative stress response. Genes Dev 19 : 2278–2283.

69. AballayA, DrenkardE, HilbunLR, AusubelFM (2003) Caenorhabditis elegans innate immune response triggered by Salmonella enterica requires intact LPS and is mediated by a MAPK signaling pathway. Curr Biol 13 : 47–52.

70. RichardsonCE, KinkelS, KimDH (2011) Physiological IRE-1-XBP-1 and PEK-1 signaling in Caenorhabditis elegans larval development and immunity. PLoS Genet 7: e1002391.

71. HuF, PadukkavidanaT, VægterCB, BradyOA, ZhengY, et al. (2010) Sortilin-Mediated Endocytosis Determines Levels of the Frontotemporal Dementia Protein, Progranulin. Neuron 68 : 654–667.

72. ReddienPW, HorvitzHR (2000) CED-2/CrkII and CED-10/Rac control phagocytosis and cell migration in Caenorhabditis elegans. Nat Cell Biol 2 : 131–136.

73. HaskinsKA, RussellJF, GaddisN, DressmanHK, AballayA (2008) Unfolded protein response genes regulated by CED-1 are required for Caenorhabditis elegans innate immunity. Dev Cell 15 : 87–97.

74. SunJ, SinghV, Kajino-SakamotoR, AballayA (2011) Neuronal GPCR controls innate immunity by regulating noncanonical unfolded protein response genes. Science 332 : 729–732.

75. YeretssianG, CorreaRG, DoironK, FitzgeraldP, DillonCP, et al. (2011) Non-apoptotic role of BID in inflammation and innate immunity. Nature 474 : 96–99.

76. BurguillosMA, DeierborgT, KavanaghE, PerssonA, HajjiN, et al. (2010) Caspase signalling controls microglia activation and neurotoxicity. Nature 472 : 319–324.

77. de CalignonA, FoxLM, PitstickR, CarlsonGA, BacskaiBJ, et al. (2011) Caspase activation precedes and leads to tangles. Nature 464 : 1201–1204.

78. GuC, ShababM, StrasserR, WoltersPJ, ShindoT, et al. (2012) Post-translational regulation and trafficking of the granulin-containing protease RD21 of Arabidopsis thaliana. PLoS One 7: e32422.

79. YamadaK, MatsushimaR, NishimuraM, Hara-NishimuraI (2001) A slow maturation of a cysteine protease with a granulin domain in the vacuoles of senescing Arabidopsis leaves. Plant Physiol 127 : 1626–1634.

80. KoizumiM, Yamaguchi-ShinozakiK, TsujiH, ShinozakiK (1993) Structure and expression of two genes that encode distinct drought-inducible cysteine proteinases in Arabidopsis thaliana. Gene 129 : 175–182.

81. BrennerS (1974) The genetics of Caenorhabditis elegans. Genetics 77 : 71–94.

82. FrankCA, BaumPD, GarrigaG (2003) HLH-14 is a C. elegans achaete-scute protein that promotes neurogenesis through asymmetric cell division. Development 130 : 6507–6518.

83. LamitinaST, MorrisonR, MoeckelGW, StrangeK (2004) Adaptation of the nematode Caenorhabditis elegans to extreme osmotic stress. Am J Physiol Cell Physiol 286: C785–791.

84. SchusterE, McElweeJJ, TulletJM, DoonanR, MatthijssensF, et al. (2010) DamID in C. elegans reveals longevity-associated targets of DAF-16/FoxO. Mol Syst Biol 6 : 399.

85. MurphyCT, McCarrollSA, BargmannCI, FraserA, KamathRS, et al. (2003) Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 424 : 277–283.