#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Innate immune signaling in Drosophila shifts anabolic lipid metabolism from triglyceride storage to phospholipid synthesis to support immune function


Autoři: Brittany A. Martínez aff001;  Rosalie G. Hoyle aff002;  Scott Yeudall aff002;  Mitchell E. Granade aff001;  Thurl E. Harris aff001;  J. David Castle aff004;  Norbert Leitinger aff001;  Michelle L. Bland aff001
Působiště autorů: Biomedical Sciences Graduate Program, University of Virginia, Charlottesville, VA, United States of America aff001;  Department of Pharmacology, University of Virginia, Charlottesville, VA, United States of America aff002;  Medical Scientist Training Program, University of Virginia, Charlottesville, VA, United States of America aff003;  Department of Cell Biology, University of Virginia, Charlottesville, VA, United States of America aff004
Vyšlo v časopise: Innate immune signaling in Drosophila shifts anabolic lipid metabolism from triglyceride storage to phospholipid synthesis to support immune function. PLoS Genet 16(11): e1009192. doi:10.1371/journal.pgen.1009192
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1009192

Souhrn

During infection, cellular resources are allocated toward the metabolically-demanding processes of synthesizing and secreting effector proteins that neutralize and kill invading pathogens. In Drosophila, these effectors are antimicrobial peptides (AMPs) that are produced in the fat body, an organ that also serves as a major lipid storage depot. Here we asked how activation of Toll signaling in the larval fat body perturbs lipid homeostasis to understand how cells meet the metabolic demands of the immune response. We find that genetic or physiological activation of fat body Toll signaling leads to a tissue-autonomous reduction in triglyceride storage that is paralleled by decreased transcript levels of the DGAT homolog midway, which carries out the final step of triglyceride synthesis. In contrast, Kennedy pathway enzymes that synthesize membrane phospholipids are induced. Mass spectrometry analysis revealed elevated levels of major phosphatidylcholine and phosphatidylethanolamine species in fat bodies with active Toll signaling. The ER stress mediator Xbp1 contributed to the Toll-dependent induction of Kennedy pathway enzymes, which was blunted by deleting AMP genes, thereby reducing secretory demand elicited by Toll activation. Consistent with ER stress induction, ER volume is expanded in fat body cells with active Toll signaling, as determined by transmission electron microscopy. A major functional consequence of reduced Kennedy pathway induction is an impaired immune response to bacterial infection. Our results establish that Toll signaling induces a shift in anabolic lipid metabolism to favor phospholipid synthesis and ER expansion that may serve the immediate demand for AMP synthesis and secretion but with the long-term consequence of insufficient nutrient storage.

Klíčová slova:

Drosophila melanogaster – Enterococcus infections – Fats – Gene expression – Immune response – Larvae – Phospholipids – Phospholipid signaling cascade


Zdroje

1. Corrigan JJ, Fonseca MT, Flatow EA, Lewis K, Steiner AA. Hypometabolism and hypothermia in the rat model of endotoxic shock: independence of circulatory hypoxia. J Physiol (Lond). 2014;592: 3901–3916. doi: 10.1113/jphysiol.2014.277277 24951620

2. Ganeshan K, Nikkanen J, Man K, Leong YA, Sogawa Y, Maschek JA, et al. Energetic Trade-Offs and Hypometabolic States Promote Disease Tolerance. Cell. 2019;177: 399–413.e12. doi: 10.1016/j.cell.2019.01.050 30853215

3. Chang C-H, Curtis JD, Maggi LB, Faubert B, Villarino AV, O’Sullivan D, et al. Posttranscriptional control of T cell effector function by aerobic glycolysis. Cell. 2013;153: 1239–1251. doi: 10.1016/j.cell.2013.05.016 23746840

4. Gleeson LE, Sheedy FJ, Palsson-McDermott EM, Triglia D, O'Leary SM, O'Sullivan MP, et al. Cutting Edge: Mycobacterium tuberculosis Induces Aerobic Glycolysis in Human Alveolar Macrophages That Is Required for Control of Intracellular Bacillary Replication. J Immunol. American Association of Immunologists; 2016;196: 2444–2449. doi: 10.4049/jimmunol.1501612 26873991

5. Krawczyk CM, Holowka T, Sun J, Blagih J, Amiel E, DeBerardinis RJ, et al. Toll-like receptor-induced changes in glycolytic metabolism regulate dendritic cell activation. Blood. 2010;115: 4742–4749. doi: 10.1182/blood-2009-10-249540 20351312

6. Krejčová G, Danielová A, Nedbalová P, Kazek M, Strych L, Chawla G, et al. Drosophila macrophages switch to aerobic glycolysis to mount effective antibacterial defense. Elife. 2019;8: 102. doi: 10.7554/eLife.50414 31609200

7. Everts B, Amiel E, Huang SC-C, Smith AM, Chang C-H, Lam WY, et al. TLR-driven early glycolytic reprogramming via the kinases TBK1-IKKɛ supports the anabolic demands of dendritic cell activation. Nat Immunol. Nature Publishing Group; 2014;15: 323–332. doi: 10.1038/ni.2833 24562310

8. van Anken E, Romijn EP, Maggioni C, Mezghrani A, Sitia R, Braakman I, et al. Sequential waves of functionally related proteins are expressed when B cells prepare for antibody secretion. Immunity. 2003;18: 243–253. doi: 10.1016/s1074-7613(03)00024-4 12594951

9. Fagone P, Sriburi R, Ward-Chapman C, Frank M, Wang J, Gunter C, et al. Phospholipid biosynthesis program underlying membrane expansion during B-lymphocyte differentiation. J Biol Chem. American Society for Biochemistry and Molecular Biology; 2007;282: 7591–7605. doi: 10.1074/jbc.M608175200 17213195

10. McGehee AM, Dougan SK, Klemm EJ, Shui G, Park B, Kim Y-M, et al. XBP-1-deficient plasmablasts show normal protein folding but altered glycosylation and lipid synthesis. The Journal of Immunology. 2009;183: 3690–3699. doi: 10.4049/jimmunol.0900953 19710472

11. Reimold AM, Iwakoshi NN, Manis J, Vallabhajosyula P, Szomolanyi-Tsuda E, Gravallese EM, et al. Plasma cell differentiation requires the transcription factor XBP-1. Nature. 2001;412: 300–307. doi: 10.1038/35085509 11460154

12. Martinon F, Chen X, Lee A-H, Glimcher LH. TLR activation of the transcription factor XBP1 regulates innate immune responses in macrophages. Nat Immunol. 2010;11: 411–418. doi: 10.1038/ni.1857 20351694

13. Tian Y, Pate C, Andreolotti A, Wang L, Tuomanen E, Boyd K, et al. Cytokine secretion requires phosphatidylcholine synthesis. J Cell Biol. Rockefeller University Press; 2008;181: 945–957. doi: 10.1083/jcb.200706152 18559668

14. Buchon N, Silverman N, Cherry S. Immunity in Drosophila melanogaster—from microbial recognition to whole-organism physiology. Nat Rev Immunol. 2014;14: 796–810. doi: 10.1038/nri3763 25421701

15. Valanne S, Wang J-H, Rämet M. The Drosophila Toll signaling pathway. J Immunol. 2011;186: 649–656. doi: 10.4049/jimmunol.1002302 21209287

16. Fehlbaum P, Bulet P, Michaut L, Lagueux M, Broekaert WF, Hetru C, et al. Insect immunity. Septic injury of Drosophila induces the synthesis of a potent antifungal peptide with sequence homology to plant antifungal peptides. J Biol Chem. 1994;269: 33159–33163. 7806546

17. Hanson MA, Dostálová A, Ceroni C, Poidevin M, Kondo S, Lemaitre B. Synergy and remarkable specificity of antimicrobial peptides in vivo using a systematic knockout approach. Elife. 2019;8: 511. doi: 10.7554/eLife.44341 30803481

18. Arrese EL, Soulages JL. Insect Fat Body: Energy, Metabolism, and Regulation. Annu Rev Entomol. 2010;55: 207–225. doi: 10.1146/annurev-ento-112408-085356 19725772

19. Lehmann M. Endocrine and physiological regulation of neutral fat storage in Drosophila. Mol Cell Endocrinol. 2018;461: 165–177. doi: 10.1016/j.mce.2017.09.008 28893568

20. Dionne MS, Pham LN, Shirasu-Hiza M, Schneider DS. Akt and FOXO dysregulation contribute to infection-induced wasting in Drosophila. Curr Biol. 2006;16: 1977–1985. doi: 10.1016/j.cub.2006.08.052 17055976

21. Péan CB, Schiebler M, Tan SWS, Sharrock JA, Kierdorf K, Brown KP, et al. Regulation of phagocyte triglyceride by a STAT-ATG2 pathway controls mycobacterial infection. Nat Commun. Nature Publishing Group; 2017;8: 14642. doi: 10.1038/ncomms14642 28262681

22. Franchet A, Niehus S, Caravello G, Ferrandon D. Phosphatidic acid as a limiting host metabolite for the proliferation of the microsporidium Tubulinosema ratisbonensis in Drosophila flies. Nat Microbiol. Nature Publishing Group; 2019;4: 645–655. doi: 10.1038/s41564-018-0344-y 30692666

23. Davoodi S, Galenza A, Panteluk A, Deshpande R, Ferguson M, Grewal S, et al. The Immune Deficiency Pathway Regulates Metabolic Homeostasis in Drosophila. The Journal of Immunology. 2019;202: 2747–2759. doi: 10.4049/jimmunol.1801632 30902902

24. DiAngelo JR, Bland ML, Bambina S, Cherry S, Birnbaum MJ. The immune response attenuates growth and nutrient storage in Drosophila by reducing insulin signaling. Proc Natl Acad Sci USA. 2009;106: 20853–20858. doi: 10.1073/pnas.0906749106 19861550

25. Roth SW, Bitterman MD, Birnbaum MJ, Bland ML. Innate Immune Signaling in Drosophila Blocks Insulin Signaling by Uncoupling PI(3,4,5)P3 Production and Akt Activation. CellReports. 2018;22: 2550–2556. doi: 10.1016/j.celrep.2018.02.033 29514084

26. Suzawa M, Muhammad NM, Joseph BS, Bland ML. The Toll Signaling Pathway Targets the Insulin-like Peptide Dilp6 to Inhibit Growth in Drosophila. CellReports. 2019;28: 1439–1446.e5. doi: 10.1016/j.celrep.2019.07.015 31390559

27. Issa N, Guillaumot N, Lauret E, Matt N, Schaeffer-Reiss C, van Dorsselaer A, et al. The Circulating Protease Persephone Is an Immune Sensor for Microbial Proteolytic Activities Upstream of the Drosophila Toll Pathway. Mol Cell. 2018;69: 539–550.e6. doi: 10.1016/j.molcel.2018.01.029 29452635

28. Kenmoku H, Hori A, Kuraishi T, Kurata S. A novel mode of induction of the humoral innate immune response in Drosophila larvae. Dis Model Mech. The Company of Biologists Ltd; 2017;10: 271–281. doi: 10.1242/dmm.027102 28250052

29. Lemaitre B, Reichhart JM, Hoffmann JA. Drosophila host defense: differential induction of antimicrobial peptide genes after infection by various classes of microorganisms. Proc Natl Acad Sci USA. 1997;94: 14614–14619. doi: 10.1073/pnas.94.26.14614 9405661

30. Ferrandon D, Jung AC, Criqui M, Lemaitre B, Uttenweiler-Joseph S, Michaut L, et al. A drosomycin-GFP reporter transgene reveals a local immune response in Drosophila that is not dependent on the Toll pathway. EMBO J. 1998;17: 1217–1227. doi: 10.1093/emboj/17.5.1217 9482719

31. Storelli G, Nam H-J, Simcox J, Villanueva CJ, Thummel CS. Drosophila HNF4 Directs a Switch in Lipid Metabolism that Supports the Transition to Adulthood. Dev Cell. 2019;48: 200–214.e6. doi: 10.1016/j.devcel.2018.11.030 30554999

32. Yamada T, Habara O, Kubo H, Nishimura T. Fat body glycogen serves as a metabolic safeguard for the maintenance of sugar levels in Drosophila. Development. Oxford University Press for The Company of Biologists Limited; 2018;145: dev158865. doi: 10.1242/dev.158865 29467247

33. Wang Y, Viscarra J, Kim S-J, Sul HS. Transcriptional regulation of hepatic lipogenesis. Nat Rev Mol Cell Biol. Nature Publishing Group; 2015;16: 678–689. doi: 10.1038/nrm4074 26490400

34. Beller M, Bulankina AV, Hsiao H-H, Urlaub H, Jäckle H, Kühnlein RP. PERILIPIN-Dependent Control of Lipid Droplet Structure and Fat Storage in Drosophila. Cell Metabolism. Elsevier Inc; 2010;12: 521–532. doi: 10.1016/j.cmet.2010.10.001 21035762

35. Grillet M, Dominguez Gonzalez B, Sicart A, Pöttler M, Cascalho A, Billion K, et al. Torsins Are Essential Regulators of Cellular Lipid Metabolism. Dev Cell. 2016;38: 235–247. doi: 10.1016/j.devcel.2016.06.017 27453503

36. Schmitt S, Ugrankar R, Greene SE, Prajapati M, Lehmann M. Drosophila Lipin interacts with insulin and TOR signaling pathways in the control of growth and lipid metabolism. J Cell Sci. 2015;128: 4395–4406. doi: 10.1242/jcs.173740 26490996

37. Ugrankar R, Liu Y, Provaznik J, Schmitt S, Lehmann M. Lipin is a central regulator of adipose tissue development and function in Drosophila melanogaster. Mol Cell Biol. 2011;31: 1646–1656. doi: 10.1128/MCB.01335-10 21300783

38. Carvalho M, Sampaio JL, Palm W, Brankatschk M, Eaton S, Shevchenko A. Effects of diet and development on the Drosophila lipidome. Mol Syst Biol. 2012;8. doi: 10.1038/msb.2012.29 22864382

39. Guan XL, Cestra G, Shui G, Kuhrs A, Schittenhelm RB, Hafen E, et al. Biochemical Membrane Lipidomics during Drosophila Development. Dev Cell. Elsevier Inc; 2013;24: 98–111. doi: 10.1016/j.devcel.2012.11.012 23260625

40. Palm W, Sampaio JL, Brankatschk M, Carvalho M, Mahmoud A, Shevchenko A, et al. Lipoproteins in Drosophila melanogaster—Assembly, Function, and Influence on Tissue Lipid Composition. P Kühnlein R, editor. PLoS Genet. 2012;8: e1002828. doi: 10.1371/journal.pgen.1002828 22844248

41. Dobrosotskaya IY, Seegmiller AC, Brown MS, Goldstein JL, Rawson RB. Regulation of SREBP processing and membrane lipid production by phospholipids in Drosophila. Science (New York, NY). American Association for the Advancement of Science; 2002;296: 879–883. doi: 10.1126/science.1071124 11988566

42. Horton JD, Goldstein JL, Brown MS. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest. American Society for Clinical Investigation; 2002;109: 1125–1131. doi: 10.1172/JCI15593 11994399

43. Sriburi R, Jackowski S, Mori K, Brewer JW. XBP1: a link between the unfolded protein response, lipid biosynthesis, and biogenesis of the endoplasmic reticulum. J Cell Biol. 2004;167: 35–41. doi: 10.1083/jcb.200406136 15466483

44. Cox JS, Walter P. A novel mechanism for regulating activity of a transcription factor that controls the unfolded protein response. Cell. 1996;87: 391–404. doi: 10.1016/s0092-8674(00)81360-4 8898193

45. Plongthongkum N, Kullawong N, Panyim S, Tirasophon W. Ire1 regulated XBP1 mRNA splicing is essential for the unfolded protein response (UPR) in Drosophila melanogaster. Biochem Biophys Res Commun. 2007;354: 789–794. doi: 10.1016/j.bbrc.2007.01.056 17266933

46. Ryoo HD, Domingos PM, Kang M-J, Steller H. Unfolded protein response in a Drosophila model for retinal degeneration. EMBO J. 2007;26: 242–252. doi: 10.1038/sj.emboj.7601477 17170705

47. Hetz C. The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat Rev Mol Cell Biol. 2012;13: 89–102. doi: 10.1038/nrm3270 22251901

48. Dong H, Adams NM, Xu Y, Cao J, Allan DSJ, Carlyle JR, et al. The IRE1 endoplasmic reticulum stress sensor activates natural killer cell immunity in part by regulating c-Myc. Nat Immunol. 2019;20: 865–878. doi: 10.1038/s41590-019-0388-z 31086333

49. Pan Y, Ballance H, Meng H, Gonzalez N, Kim S-M, Abdurehman L, et al. 12-h clock regulation of genetic information flow by XBP1s. PLoS Biol. 2020;18: e3000580. doi: 10.1371/journal.pbio.3000580 31935211

50. Shandala T, Woodcock JM, Ng Y, Biggs L, Skoulakis EMC, Brooks DA, et al. Drosophila 14-3-3ε has a crucial role in anti-microbial peptide secretion and innate immunity. J Cell Sci. 2011;124: 2165–2174. doi: 10.1242/jcs.080598 21670199

51. Clemmons AW, Lindsay SA, Wasserman SA. An effector Peptide family required for Drosophila Toll-mediated immunity. PLoS Pathog. 2015;11: e1004876. doi: 10.1371/journal.ppat.1004876 25915418

52. Cohen LB, Lindsay SA, Xu Y, Lin SJH, Wasserman SA. The Daisho Peptides Mediate Drosophila Defense Against a Subset of Filamentous Fungi. Front Immunol. Frontiers; 2020;11: 9. doi: 10.3389/fimmu.2020.00009 32038657

53. Fu S, Yang L, Li P, Hofmann O, Dicker L, Hide W, et al. Aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity. Nature. Nature Publishing Group; 2011;473: 528–531. doi: 10.1038/nature09968 21532591

54. Hou NS, Gutschmidt A, Choi DY, Pather K, Shi X, Watts JL, et al. Activation of the endoplasmic reticulum unfolded protein response by lipid disequilibrium without disturbed proteostasis in vivo. Proc Natl Acad Sci USA. 2014;111: E2271–80. doi: 10.1073/pnas.1318262111 24843123

55. Broderick NA, Lemaitre B. Gut-associated microbes of Drosophila melanogaster. Gut Microbes. 2012;3: 307–321. doi: 10.4161/gmic.19896 22572876

56. Fullerton MD, Hakimuddin F, Bonen A, Bakovic M. The development of a metabolic disease phenotype in CTP:phosphoethanolamine cytidylyltransferase-deficient mice. Journal of Biological Chemistry. American Society for Biochemistry and Molecular Biology; 2009;284: 25704–25713. doi: 10.1074/jbc.M109.023846 19625253

57. Guo Y, Walther TC, Rao M, Stuurman N, Goshima G, Terayama K, et al. Functional genomic screen reveals genes involved in lipid-droplet formation and utilization. Nature. 2008;453: 657–661. doi: 10.1038/nature06928 18408709

58. Leonardi R, Frank MW, Jackson PD, Rock CO, Jackowski S. Elimination of the CDP-ethanolamine pathway disrupts hepatic lipid homeostasis. Journal of Biological Chemistry. American Society for Biochemistry and Molecular Biology; 2009;284: 27077–27089. doi: 10.1074/jbc.M109.031336 19666474

59. Lim HY, Wang W, Wessells RJ, Ocorr K, Bodmer R. Phospholipid homeostasis regulates lipid metabolism and cardiac function through SREBP signaling in Drosophila. Genes Dev. Cold Spring Harbor Lab; 2011;25: 189–200. doi: 10.1101/gad.1992411 21245170

60. Walker AK, Jacobs RL, Watts JL, Rottiers V, Jiang K, Finnegan DM, et al. A conserved SREBP-1/phosphatidylcholine feedback circuit regulates lipogenesis in metazoans. Cell. 2011;147: 840–852. doi: 10.1016/j.cell.2011.09.045 22035958

61. Harris CA, Haas JT, Streeper RS, Stone SJ, Kumari M, Yang K, et al. DGAT enzymes are required for triacylglycerol synthesis and lipid droplets in adipocytes. J Lipid Res. American Society for Biochemistry and Molecular Biology; 2011;52: 657–667. doi: 10.1194/jlr.M013003 21317108

62. Yang C, Wang X, Wang J, Wang X, Chen W, Lu N, et al. Rewiring Neuronal Glycerolipid Metabolism Determines the Extent of Axon Regeneration. Neuron. 2020;105: 276–292.e5. doi: 10.1016/j.neuron.2019.10.009 31786011

63. Harris TE, Finck BN. Dual function lipin proteins and glycerolipid metabolism. Trends in Endocrinology & Metabolism. 2011;22: 226–233. doi: 10.1016/j.tem.2011.02.006 21470873

64. Harris TE, Huffman TA, Chi A, Shabanowitz J, Hunt DF, Kumar A, et al. Insulin controls subcellular localization and multisite phosphorylation of the phosphatidic acid phosphatase, lipin 1. J Biol Chem. American Society for Biochemistry and Molecular Biology; 2007;282: 277–286. doi: 10.1074/jbc.M609537200 17105729

65. Cornell RB, Ridgway ND. CTP:phosphocholine cytidylyltransferase: Function, regulation, and structure of an amphitropic enzyme required for membrane biogenesis. Progress in Lipid Research. 2015;59: 147–171. doi: 10.1016/j.plipres.2015.07.001 26165797

66. Infante JP. Rate-limiting steps in the cytidine pathway for the synthesis of phosphatidylcholine and phosphatidylethanolamine. Biochemical Journal. 1977;167: 847–849. doi: 10.1042/bj1670847 603639

67. Kirk SJ, Cliff JM, Thomas JA, Ward TH. Biogenesis of secretory organelles during B cell differentiation. J Leukoc Biol. Society for Leukocyte Biology; 2010;87: 245–255. doi: 10.1189/jlb.1208774 19889725

68. Sriburi R, Bommiasamy H, Buldak GL, Robbins GR, Frank M, Jackowski S, et al. Coordinate regulation of phospholipid biosynthesis and secretory pathway gene expression in XBP-1(S)-induced endoplasmic reticulum biogenesis. J Biol Chem. 2007;282: 7024–7034. doi: 10.1074/jbc.M609490200 17213183

69. Rosen DA, Seki SM, Fernández-Castañeda A, Beiter RM, Eccles JD, Woodfolk JA, et al. Modulation of the sigma-1 receptor-IRE1 pathway is beneficial in preclinical models of inflammation and sepsis. Sci Transl Med. 2019;11: eaau5266. doi: 10.1126/scitranslmed.aau5266 30728287

70. Nyako M, Marks C, Sherma J, Reynolds ER. Tissue-specific and developmental effects of the easily shocked mutation on ethanolamine kinase activity and phospholipid composition in Drosophila melanogaster. Biochem Genet. Kluwer Academic Publishers-Plenum Publishers; 2001;39: 339–349. doi: 10.1023/a:1012209030803 11758729

71. Weber U, Eroglu C, Mlodzik M. Phospholipid membrane composition affects EGF receptor and Notch signaling through effects on endocytosis during Drosophila development. Dev Cell. 2003;5: 559–570. doi: 10.1016/s1534-5807(03)00273-9 14536058

72. Meltzer S, Bagley JA, Perez GL, O'Brien CE, DeVault L, Guo Y, et al. Phospholipid Homeostasis Regulates Dendrite Morphogenesis in Drosophila Sensory Neurons. CellReports. 2017;21: 859–866. doi: 10.1016/j.celrep.2017.09.089 29069593

73. Pavlidis P, Ramaswami M, Tanouye MA. The Drosophila easily shocked gene: a mutation in a phospholipid synthetic pathway causes seizure, neuronal failure, and paralysis. Cell. 1994;79: 23–33. doi: 10.1016/0092-8674(94)90397-2 7923374

74. Gupta T, Schüpbach T. Cct1, a phosphatidylcholine biosynthesis enzyme, is required for Drosophila oogenesis and ovarian morphogenesis. Development. Oxford University Press for The Company of Biologists Limited; 2003;130: 6075–6087. doi: 10.1242/dev.00817 14597574

75. Hu X, Yagi Y, Tanji T, Zhou S, Ip YT. Multimerization and interaction of Toll and Spätzle in Drosophila. Proc Natl Acad Sci USA. National Acad Sciences; 2004;101: 9369–9374. doi: 10.1073/pnas.0307062101 15197269

76. Yagi Y, Ip YT. Helicase89B is a Mot1p/BTAF1 homologue that mediates an antimicrobial response in Drosophila. EMBO Rep. EMBO Press; 2005;6: 1088–1094. doi: 10.1038/sj.embor.7400542 16200050

77. Hiroyasu A, DeWitt DC, Goodman AG. Extraction of Hemocytes from Drosophila melanogaster Larvae for Microbial Infection and Analysis. J Vis Exp. 2018. doi: 10.3791/57077 29889203

78. Pascual A, Chaminade M, Preat T. Ethanolamine kinase controls neuroblast divisions in Drosophila mushroom bodies. Dev Biol. 2005;280: 177–186. doi: 10.1016/j.ydbio.2005.01.017 15766757

79. Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008;3: 1101–1108. doi: 10.1038/nprot.2008.73 18546601

80. Boroda S, Takkellapati S, Lawrence RT, Entwisle SW, Pearson JM, Granade ME, et al. The phosphatidic acid-binding, polybasic domain is responsible for the differences in the phosphoregulation of lipins 1 and 3. Journal of Biological Chemistry. American Society for Biochemistry and Molecular Biology; 2017;292: 20481–20493. doi: 10.1074/jbc.M117.786574 28982975

81. Han G-S, Carman GM. Assaying lipid phosphate phosphatase activities. Methods Mol Biol. New Jersey: Humana Press; 2004;284: 209–216. doi: 10.1385/1-59259-816-1:209 15173618

82. Bligh EG, Dyer WJ. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959;37: 911–917. doi: 10.1139/o59-099 13671378

83. Serbulea V, Upchurch CM, Schappe MS, Voigt P, DeWeese DE, Desai BN, et al. Macrophage phenotype and bioenergetics are controlled by oxidized phospholipids identified in lean and obese adipose tissue. Proc Natl Acad Sci USA. 2018;115: E6254–E6263. doi: 10.1073/pnas.1800544115 29891687

84. Tschanz SA, Burri PH, Weibel ER. A simple tool for stereological assessment of digital images: the STEPanizer. J Microsc. John Wiley & Sons, Ltd (10.1111); 2011;243: 47–59. doi: 10.1111/j.1365-2818.2010.03481.x 21375529

85. Weibel ER, Kistler GS, Scherle WF. PRACTICAL STEREOLOGICAL METHODS FOR MORPHOMETRIC CYTOLOGY. J Cell Biol. Rockefeller University Press; 1966;30: 23–38. doi: 10.1083/jcb.30.1.23 5338131


Článek vyšel v časopise

PLOS Genetics


2020 Číslo 11
Nejčtenější tento týden
Nejčtenější v tomto čísle
Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

Důležitost adherence při depresivním onemocnění
nový kurz
Autoři: MUDr. Eliška Bartečková, Ph.D.

Koncepce osteologické péče pro gynekology a praktické lékaře
Autoři: MUDr. František Šenk

Sekvenční léčba schizofrenie
Autoři: MUDr. Jana Hořínková, Ph.D.

Hypertenze a hypercholesterolémie – synergický efekt léčby
Autoři: prof. MUDr. Hana Rosolová, DrSc.

Multidisciplinární zkušenosti u pacientů s diabetem
Autoři: Prof. MUDr. Martin Haluzík, DrSc., prof. MUDr. Vojtěch Melenovský, CSc., prof. MUDr. Vladimír Tesař, DrSc.

Všechny kurzy
Přihlášení
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

#ADS_BOTTOM_SCRIPTS#