Cells in the C. elegans germline undergo programmed cell death as part of the normal developmental program and in response to various stresses. Here, we discovered that more germ cells undergo programmed cell death under stress conditions associated with the accumulation of misfolded proteins in the endoplasmic reticulum, a cellular organelle responsible for protein folding and trafficking. Surprisingly, we found that germ cell death is a consequence of stress in neurons rather than in the germ cells themselves. This implies that germ cell death under ER stress conditions is regulated at the organismal level and implicates signaling between tissues.
Vyšlo v časopise: It's All in Your Mind: Determining Germ Cell Fate by Neuronal IRE-1 in. PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004747 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004747
1. JudyME, NakamuraA, HuangA, GrantH, McCurdyH, et al. (2013) A shift to organismal stress resistance in programmed cell death mutants. PLoS Genet 9: e1003714.
2. KerrJF, WyllieAH, CurrieAR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26 : 239–257.
3. FuldaS, DebatinKM (2006) Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene 25 : 4798–4811.
4. SulstonJE, HorvitzHR (1977) Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Dev Biol 56 : 110–156.
5. SulstonJE, SchierenbergE, WhiteJG, ThomsonJN (1983) The embryonic cell lineage of the nematode Caenorhabditis elegans. Dev Biol 100 : 64–119.
6. GumiennyTL, LambieE, HartwiegE, HorvitzHR, HengartnerMO (1999) Genetic control of programmed cell death in the Caenorhabditis elegans hermaphrodite germline. Development 126 : 1011–1022.
7. SalinasLS, MaldonadoE, NavarroRE (2006) Stress-induced germ cell apoptosis by a p53 independent pathway in Caenorhabditis elegans. Cell Death Differ 13 : 2129–2139.
8. AballayA, AusubelFM (2001) Programmed cell death mediated by ced-3 and ced-4 protects Caenorhabditis elegans from Salmonella typhimurium-mediated killing. Proc Natl Acad Sci U S A 98 : 2735–2739.
9. 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.
10. KimbleJE, WhiteJG (1981) On the control of germ cell development in Caenorhabditis elegans. Dev Biol 81 : 208–219.
11. AnduxS, EllisRE (2008) Apoptosis maintains oocyte quality in aging Caenorhabditis elegans females. PLoS Genet 4: e1000295.
12. LuoS, KleemannGA, AshrafJM, ShawWM, MurphyCT (2010) TGF-beta and insulin signaling regulate reproductive aging via oocyte and germline quality maintenance. Cell 143 : 299–312.
13. EllisHM, HorvitzHR (1986) Genetic control of programmed cell death in the nematode C. elegans. Cell 44 : 817–829.
14. HengartnerMO, HorvitzHR (1994) C. elegans cell survival gene ced-9 encodes a functional homolog of the mammalian proto-oncogene bcl-2. Cell 76 : 665–676.
15. YuanJ, HorvitzHR (1992) The Caenorhabditis elegans cell death gene ced-4 encodes a novel protein and is expressed during the period of extensive programmed cell death. Development 116 : 309–320.
16. 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.
17. DerryWB, PutzkeAP, RothmanJH (2001) Caenorhabditis elegans p53: role in apoptosis, meiosis, and stress resistance. Science 294 : 591–595.
18. SchumacherB, HofmannK, BoultonS, GartnerA (2001) The C. elegans homolog of the p53 tumor suppressor is required for DNA damage-induced apoptosis. Curr Biol 11 : 1722–1727.
19. SchumacherB, SchertelC, WittenburgN, TuckS, MitaniS, et al. (2005) C. elegans ced-13 can promote apoptosis and is induced in response to DNA damage. Cell Death Differ 12 : 153–161.
20. YoshidaH (2007) ER stress and diseases. Febs J 274 : 630–658.
21. RonD, WalterP (2007) Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 8 : 519–529.
22. CalfonM, ZengH, UranoF, TillJH, HubbardSR, et al. (2002) IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature 415 : 92–96.
23. 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.
24. YoshidaH, MatsuiT, YamamotoA, OkadaT, MoriK (2001) XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell 107 : 881–891.
25. RichardsonCE, KinkelS, KimDH (2011) Physiological IRE-1-XBP-1 and PEK-1 signaling in Caenorhabditis elegans larval development and immunity. PLoS Genet 7: e1002391.
26. SafraM, Ben-HamoS, KenyonC, Henis-KorenblitS (2013) The ire-1 ER stress-response pathway is required for normal secretory-protein metabolism in C. elegans. J Cell Sci 126 : 4136–4146.
27. GormanAM, HealySJ, JagerR, SamaliA (2012) Stress management at the ER: regulators of ER stress-induced apoptosis. Pharmacol Ther 134 : 306–316.
28. TabasI, RonD (2011) Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat Cell Biol 13 : 184–190.
29. UranoF, WangX, BertolottiA, ZhangY, ChungP, et al. (2000) Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 287 : 664–666.
30. YonedaT, ImaizumiK, OonoK, YuiD, GomiF, et al. (2001) Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, through tumor necrosis factor receptor-associated factor 2-dependent mechanism in response to the ER stress. J Biol Chem 276 : 13935–13940.
31. HanD, LernerAG, Vande WalleL, UptonJP, XuW, et al. (2009) IRE1alpha kinase activation modes control alternate endoribonuclease outputs to determine divergent cell fates. Cell 138 : 562–575.
32. HollienJ, WeissmanJS (2006) Decay of endoplasmic reticulum-localized mRNAs during the unfolded protein response. Science 313 : 104–107.
33. OgataM, HinoS, SaitoA, MorikawaK, KondoS, et al. (2006) Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol 26 : 9220–9231.
34. WitteK, SchuhAL, HegermannJ, SarkeshikA, MayersJR, et al. (2011) TFG-1 function in protein secretion and oncogenesis. Nat Cell Biol 13 : 550–558.
35. ChenL, McCloskeyT, JoshiPM, RothmanJH (2008) ced-4 and proto-oncogene tfg-1 antagonistically regulate cell size and apoptosis in C. elegans. Curr Biol 18 : 1025–1033.
36. ZhouZ, HartwiegE, HorvitzHR (2001) CED-1 is a transmembrane receptor that mediates cell corpse engulfment in C. elegans. Cell 104 : 43–56.
37. ItoS, GreissS, GartnerA, DerryWB (2010) Cell-nonautonomous regulation of C. elegans germ cell death by kri-1. Curr Biol 20 : 333–338.
38. HofmannER, MilsteinS, BoultonSJ, YeM, HofmannJJ, et al. (2002) Caenorhabditis elegans HUS-1 is a DNA damage checkpoint protein required for genome stability and EGL-1-mediated apoptosis. Curr Biol 12 : 1908–1918.
39. XiaoH, ChenD, FangZ, XuJ, SunX, et al. (2009) Lysosome biogenesis mediated by vps-18 affects apoptotic cell degradation in Caenorhabditis elegans. Mol Biol Cell 20 : 21–32.
40. KumstaC, HansenM (2012) C. elegans rrf-1 mutations maintain RNAi efficiency in the soma in addition to the germline. PLoS One 7: e35428.
41. TijstermanM, OkiharaKL, ThijssenK, PlasterkRH (2002) PPW-1, a PAZ/PIWI protein required for efficient germline RNAi, is defective in a natural isolate of C. elegans. Curr Biol 12 : 1535–1540.
42. DalfoD, MichaelsonD, HubbardEJ (2012) Sensory regulation of the C. elegans germline through TGF-beta-dependent signaling in the niche. Curr Biol 22 : 712–719.
43. KulalertW, KimDH (2013) The unfolded protein response in a pair of sensory neurons promotes entry of C. elegans into dauer diapause. Curr Biol 23 : 2540–2545.
44. KellyWG, XuS, MontgomeryMK, FireA (1997) Distinct requirements for somatic and germline expression of a generally expressed Caernorhabditis elegans gene. Genetics 146 : 227–238.
45. KimataY, Ishiwata-KimataY, ItoT, HirataA, SuzukiT, et al. (2007) Two regulatory steps of ER-stress sensor Ire1 involving its cluster formation and interaction with unfolded proteins. J Cell Biol 179 : 75–86.
46. LiH, KorennykhAV, BehrmanSL, WalterP (2010) Mammalian endoplasmic reticulum stress sensor IRE1 signals by dynamic clustering. Proc Natl Acad Sci U S A 107 : 16113–16118.
47. ElliottMR, RavichandranKS (2010) Clearance of apoptotic cells: implications in health and disease. J Cell Biol 189 : 1059–1070.
48. BargmannCI, HorvitzHR (1991) Control of larval development by chemosensory neurons in Caenorhabditis elegans. Science 251 : 1243–1246.
49. RenP, LimCS, JohnsenR, AlbertPS, PilgrimD, et al. (1996) Control of C. elegans larval development by neuronal expression of a TGF-beta homolog. Science 274 : 1389–1391.
50. AlcedoJ, KenyonC (2004) Regulation of C. elegans Longevity by Specific Gustatory and Olfactory Neurons. Neuron 41 : 45–55.
51. BishopNA, GuarenteL (2007) Two neurons mediate diet-restriction-induced longevity in C. elegans. Nature 447 : 545–549.
52. SendoelA, KohlerI, FellmannC, LoweSW, HengartnerMO (2010) HIF-1 antagonizes p53-mediated apoptosis through a secreted neuronal tyrosinase. Nature 465 : 577–583.
53. 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.
54. HollienJ, LinJH, LiH, StevensN, WalterP, et al. (2009) Regulated Ire1-dependent decay of messenger RNAs in mammalian cells. J Cell Biol 186 : 323–331.
55. LipsonKL, FonsecaSG, IshigakiS, NguyenLX, FossE, et al. (2006) Regulation of insulin biosynthesis in pancreatic beta cells by an endoplasmic reticulum-resident protein kinase IRE1. Cell Metab 4 : 245–254.
56. LipsonKL, GhoshR, UranoF (2008) The role of IRE1alpha in the degradation of insulin mRNA in pancreatic beta-cells. PLoS ONE 3: e1648.
57. PirotP, NaamaneN, LibertF, MagnussonNE, OrntoftTF, et al. (2007) Global profiling of genes modified by endoplasmic reticulum stress in pancreatic beta cells reveals the early degradation of insulin mRNAs. Diabetologia 50 : 1006–1014.
58. 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.
59. ArsenovicPT, MaldonadoAT, ColleluoriVD, BlossTA (2012) Depletion of the C. elegans NAC engages the unfolded protein response, resulting in increased chaperone expression and apoptosis. PLoS One 7: e44038.
60. VermezovicJ, StergiouL, HengartnerMO, d'Adda di FagagnaF (2012) Differential regulation of DNA damage response activation between somatic and germline cells in Caenorhabditis elegans. Cell Death Differ 19 : 1847–1855.
61. AngeliS, KlangI, SivapathamR, MarkK, ZuckerD, et al. (2013) A DNA synthesis inhibitor is protective against proteotoxic stressors via modulation of fertility pathways in Caenorhabditis elegans. Aging (Albany NY) 5 : 759–769.
62. ShemeshN, ShaiN, Ben-ZviA (2013) Germline stem cell arrest inhibits the collapse of somatic proteostasis early in Caenorhabditis elegans adulthood. Aging Cell 12 : 814–822.
63. VilchezD, MorantteI, LiuZ, DouglasPM, MerkwirthC, et al. (2012) RPN-6 determines C. elegans longevity under proteotoxic stress conditions. Nature 489 : 263–268.
64. Arantes-OliveiraN, BermanJR, KenyonC (2003) Healthy animals with extreme longevity. Science 302 : 611.
65. HsinH, KenyonC (1999) Signals from the reproductive system regulate the lifespan of C. elegans. Nature 399 : 362–366.
66. DurieuxJ, WolffS, DillinA (2011) The cell-non-autonomous nature of electron transport chain-mediated longevity. Cell 144 : 79–91.
67. PrahladV, CorneliusT, MorimotoRI (2008) Regulation of the cellular heat shock response in Caenorhabditis elegans by thermosensory neurons. Science 320 : 811–814.
68. PrahladV, MorimotoRI (2011) Neuronal circuitry regulates the response of Caenorhabditis elegans to misfolded proteins. Proc Natl Acad Sci U S A 108 : 14204–14209.
69. SunJ, LiuY, AballayA (2012) Organismal regulation of XBP-1-mediated unfolded protein response during development and immune activation. EMBO Rep 13 : 855–860.
70. SunJ, SinghV, Kajino-SakamotoR, AballayA (2011) Neuronal GPCR controls innate immunity by regulating noncanonical unfolded protein response genes. Science 332 : 729–732.
71. TaylorRC, DillinA (2013) XBP-1 is a cell-nonautonomous regulator of stress resistance and longevity. Cell 153 : 1435–1447.
72. NixP, HammarlundM, HauthL, LachnitM, JorgensenEM, et al. (2014) Axon regeneration genes identified by RNAi screening in C. elegans. J Neurosci 34 : 629–645.
73. FirnhaberC, HammarlundM (2013) Neuron-specific feeding RNAi in C. elegans and its use in a screen for essential genes required for GABA neuron function. PLoS Genet 9: e1003921.
74. BulowHE, BerryKL, TopperLH, PelesE, HobertO (2002) Heparan sulfate proteoglycan-dependent induction of axon branching and axon misrouting by the Kallmann syndrome gene kal-1. Proc Natl Acad Sci U S A 99 : 6346–6351.
75. TsalikEL, NiacarisT, WenickAS, PauK, AveryL, et al. (2003) LIM homeobox gene-dependent expression of biogenic amine receptors in restricted regions of the C. elegans nervous system. Dev Biol 263 : 81–102.
76. CalixtoA, ChelurD, TopalidouI, ChenX, ChalfieM (2010) Enhanced neuronal RNAi in C. elegans using SID-1. Nat Methods 7 : 554–559.
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