Physiological IRE-1-XBP-1 and PEK-1 Signaling in Larval Development and Immunity
Endoplasmic reticulum (ER) stress activates the Unfolded Protein Response, a compensatory signaling response that is mediated by the IRE-1, PERK/PEK-1, and ATF-6 pathways in metazoans. Genetic studies have implicated roles for UPR signaling in animal development and disease, but the function of the UPR under physiological conditions, in the absence of chemical agents administered to induce ER stress, is not well understood. Here, we show that in Caenorhabditis elegans XBP-1 deficiency results in constitutive ER stress, reflected by increased basal levels of IRE-1 and PEK-1 activity under physiological conditions. We define a dynamic, temperature-dependent requirement for XBP-1 and PEK-1 activities that increases with immune activation and at elevated physiological temperatures in C. elegans. Our data suggest that the negative feedback loops involving the activation of IRE-1-XBP-1 and PEK-1 pathways serve essential roles, not only at the extremes of ER stress, but also in the maintenance of ER homeostasis under physiological conditions.
Vyšlo v časopise:
Physiological IRE-1-XBP-1 and PEK-1 Signaling in Larval Development and Immunity. PLoS Genet 7(11): e32767. doi:10.1371/journal.pgen.1002391
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1002391
Souhrn
Endoplasmic reticulum (ER) stress activates the Unfolded Protein Response, a compensatory signaling response that is mediated by the IRE-1, PERK/PEK-1, and ATF-6 pathways in metazoans. Genetic studies have implicated roles for UPR signaling in animal development and disease, but the function of the UPR under physiological conditions, in the absence of chemical agents administered to induce ER stress, is not well understood. Here, we show that in Caenorhabditis elegans XBP-1 deficiency results in constitutive ER stress, reflected by increased basal levels of IRE-1 and PEK-1 activity under physiological conditions. We define a dynamic, temperature-dependent requirement for XBP-1 and PEK-1 activities that increases with immune activation and at elevated physiological temperatures in C. elegans. Our data suggest that the negative feedback loops involving the activation of IRE-1-XBP-1 and PEK-1 pathways serve essential roles, not only at the extremes of ER stress, but also in the maintenance of ER homeostasis under physiological conditions.
Zdroje
1. MoriK 2009 Signaling pathways in the unfolded protein response: development from yeast to mammals. Journal of Biochemistry 146 743 750
2. RonDWalterP 2007 Signal integration in the endoplasmic reticulum unfolded protein response. Nature Reviews Molecular Cell Biology 8 519 529
3. SchröderMKaufmanRJ 2005 The mammalian unfolded protein response. Annual Reviews in Biochemistry 74 739 789
4. CalfonMZengHQUranoFTillJHHubbardSR 2002 IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature 415 92 96
5. ShamuCEWalterP 1996 Oligomerization and phosphorylation of the Ire1p kinase during intracellular signaling from the endoplasmic reticulum to the nucleus. EMBO Journal 15 3028 3029
6. ShenXEllisRELeeKLiuC-YYangK 2001 Complementary signaling pathways regulate the unfolded protein response and are required for C. elegans development. Cell 107 893 903
7. YoshidaHMatsuiTYamamotoAOkadaTMoriK 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
8. HardingHPZhangYBertolottiAZengHRonD 2000 Perk is essential for translational regulation and cell survival during the unfolded protein response. Molecular Cell 5 897 904
9. HardingHPNovoaIZhangYZengHWekR 2000 Regulated translation initiation controls stress-induced gene expression in mammalian cells. Molecular Cell 6 1099 1108
10. YoshidaHOkadaTHazeKYanagiHYuraT 2000 ATF6 activated by proteolysis binds in the presence of NF-Y (CBF) directly to the cis-acting element responsible for the mammalian unfolded protein response. Molecular and Cellular Biology 20 6755 6767
11. LeeA-HScapaEFCohenDEGlimcherLH 2008 Regulation of hepatic lipogenesis by the transcription factor XBP1. Science 320 1492 1496
12. KaserALeeA-HFrankeAGlickmanJNZeissigS 2008 XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease. Cell 134 743 756
13. ShafferALShapiro-ShelefMIwakoshiNNZhaoHYuX 2004 XBP1, downstream of Blimp-1, expands the secretory apparatus and other organelles, and increases protein synthesis in plasma cell differentiation. Immunity 21 81 93
14. ToddDJLeeA-HGlimcherLH 2008 The endoplasmic reticulum stress response in immunity and autoimmunity. Nature Reviews Immunology 8 663 674
15. ZhangWFengDLiYLidaKMcGrathB 2006 PERK EIF2AK3 control of pancreatic beta cell differentiation and proliferation is required for postnatal glucose homeostasis. Cell Metabolism 4 491 497
16. ShenXEllisRESakakiKKaufmanRJ 2005 Genetic interactions due to constitutive and inducible gene regulation mediated by the unfolded protein response in C. elegans. PLoS Genet 1 e37 doi:10.1371/journal.pgen.0010037
17. RutkowskiDTHegdeRS 2010 Regulation of basal and cellular physiology by the homeostatic unfolded protein response. Journal of Cell Biology 189 783 794
18. ReimoldAMIwakoshiNNManisJVallabhajosyulaPSzomolanyi-TsudaE 2001 Plasma cell differentiation requires the transcription factor XBP-1. Nature 412 300 307
19. HuC-CADouganSKMcGeheeAMLoveJCPloeghHL 2009 XBP-1 regulates signal transduction, transcription factors and bone marrow colonization in B cells. EMBO Journal 28 1624 1636
20. MartinonFChenXLeeA-HGlimcherLH 2010 TLR activation of the transcription factor XBP1 regulates innate immune responses in macrophages. Nature Immunology 11 411 418
21. RichardsonCEKooistraTKimDH 2010 An essential role for XBP-1 in host protection against immune activation in C. elegans. Nature 463 1092 1095
22. RehwinkelJRaesJIzaurraldeE 2006 Nonsense-mediated mRNA decay: target genes and functional diversification of effectors. Trends in biochemical sciences 31 639 646
23. PageMFCarrBAndersKRGrimsonAAndersonP 1999 SMG-2 is a phosphorylated protein required for mRNA surveillance in Caenorhabditis elegans and related to Upf1p of yeast. Molecular and Cellular Biology 19 5943 5951
24. GardnerLB 2008 Hypoxic inhibition of nonsense-mediated RNA decay regulates gene expression and the integrated stress response. Molecular and Cellular Biology 28 3729 3741
25. HamanakaRBBennettBSCullinanSBDiehlJA 2005 PERK and GCN2 contribute to eIF2 alpha phosphorylation and cell cycle arrest after activation of the unfolded protein response pathway. Molecular Biology of the Cell 16 5493 5501
26. NukazukaAFujisawaHInadaTOdaYTakagiS 2008 Semaphorin controls epidermal morphogenesis by stimulating mRNA translation via eIF2a in Caenorhabditis elegans. Genes and Development 22 1025 1036
27. KimDHFeinbaumRAlloingGEmersonFEGarsinDA 2002 A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity. Science 297 623 626
28. BischofLJKaoC-YLosFCOGonzalezMRShenZ 2008 Activation of the Unfolded Protein Response is required for defenses against bacterial pore-forming toxin in vivo. PLoS Path 4 e100176 doi:10.1371/journal.ppat.1000176
29. KurzCLShapiraMChenKBaillieDLTanM-W 2007 Caenorhabditis elegans pgp-5 is involved in resistance to bacterial infection and heavy metal and its regulation requires TIR-1 and p38 map kinase cascade. Biochemical and Biophysical Research Communications 363 438 443
30. TroemelERChuSWReinkeVLeeSSAusubelFM 2006 p38 MAPK regulates expression of immune response genes and contributes to longevity in C. elegans. PLoS Genet 2 e183 doi:10.1371/journal.pgen.0020183
31. TroemelERFelixM-AWhitemanNKBarriereAAusubelFM 2008 Microsporidia are natural intracelular parasites of the nematode Caenorhabditis elegans. PLoS Biol 6 e309 doi:doi:10.1371/journal.pbio.0060309
32. ZinsznerHKurodaMWangXBatchvarovaNLightfootRT 1998 CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum. Genes and Development 12 982 995
33. LeeA-HHeidtmanKHotamisligilGSGlimcherLH 2011 Dual and opposing roles of the unfolded protein response regulated by IRE1alpha and XBP1 in proinsulin processing and insulin secretion. Proceedings of the National Academy of Sciences of the United States of America 108 8885 90 doi:10.1073/pnas.1105564108
34. WooCWCuiDArellanoJDorweilerBHardingHP 2009 Adaptive suppression of the ATF4-CHOP branch of the unfolded protein response by toll-like receptor signalling. Nature Cell Biology 11 1473 1480
35. BrennerS 1974 The genetics of Caenorhabditis elegans. Genetics 77 71 94
36. RasbandWS ImageJ, U.S. National Institutes of Health, Besthesda, Maryland, USA, http://imagej.nih.gov/ij/, 1997–2011
37. GariganDHsuA-LFraserAGKamathRSAhringerJ 2002 Genetic Analysis of Tissue Aging in Caenorhabditis elegans: A Role for Heat-Shock Factor and Bacterial Proliferation. Genetics 161 1101 1112
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2011 Číslo 11
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