The Motility of a Human Parasite, , Is Regulated by a Novel Lysine Methyltransferase
Protozoa in the phylum Apicomplexa are a large group of obligate intracellular parasites. Toxoplasma gondii and other apicomplexan parasites, such as Plasmodium falciparum, cause diseases by reiterating their lytic cycle, comprising host cell invasion, parasite replication, and parasite egress. The successful completion of the lytic cycle requires that the parasite senses changes in its environment and switches between the non-motile (for intracellular replication) and motile (for invasion and egress) states appropriately. Although the signaling pathway that regulates the motile state switch is critical to the pathogenesis of the diseases caused by these parasites, it is not well understood. Here we report a previously unknown mechanism of regulating the motility activation in Toxoplasma, mediated by a protein lysine methyltransferase, AKMT (for Apical complex lysine (K) methyltransferase). AKMT depletion greatly inhibits activation of motility, compromises parasite invasion and egress, and thus severely impairs the lytic cycle. Interestingly, AKMT redistributes from the apical complex to the parasite body rapidly in the presence of egress-stimulating signals that increase [Ca2+] in the parasite cytoplasm, suggesting that AKMT regulation of parasite motility might be accomplished by the precise temporal control of its localization in response to environmental changes.
Vyšlo v časopise:
The Motility of a Human Parasite, , Is Regulated by a Novel Lysine Methyltransferase. PLoS Pathog 7(9): e32767. doi:10.1371/journal.ppat.1002201
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1002201
Souhrn
Protozoa in the phylum Apicomplexa are a large group of obligate intracellular parasites. Toxoplasma gondii and other apicomplexan parasites, such as Plasmodium falciparum, cause diseases by reiterating their lytic cycle, comprising host cell invasion, parasite replication, and parasite egress. The successful completion of the lytic cycle requires that the parasite senses changes in its environment and switches between the non-motile (for intracellular replication) and motile (for invasion and egress) states appropriately. Although the signaling pathway that regulates the motile state switch is critical to the pathogenesis of the diseases caused by these parasites, it is not well understood. Here we report a previously unknown mechanism of regulating the motility activation in Toxoplasma, mediated by a protein lysine methyltransferase, AKMT (for Apical complex lysine (K) methyltransferase). AKMT depletion greatly inhibits activation of motility, compromises parasite invasion and egress, and thus severely impairs the lytic cycle. Interestingly, AKMT redistributes from the apical complex to the parasite body rapidly in the presence of egress-stimulating signals that increase [Ca2+] in the parasite cytoplasm, suggesting that AKMT regulation of parasite motility might be accomplished by the precise temporal control of its localization in response to environmental changes.
Zdroje
1. LevineND 1988 Progress in taxonomy of the Apicomplexan protozoa. J Protozool 35 518 520
2. DobrowolskiJMCarruthersVBSibleyLD 1997 Participation of myosin in gliding motility and host cell invasion by Toxoplasma gondii. Mol Microbiol 26 163 173
3. LingelbachKJoinerKA 1998 The parasitophorous vacuole membrane surrounding Plasmodium and Toxoplasma: an unusual compartment in infected cells. J Cell Sci 111 1467 1475
4. SheffieldHGMeltonML 1968 The fine structure and reproduction of Toxoplasma gondii. J Parasitol 54 209 226
5. SinaiAPJoinerKA 1997 Safe haven: the cell biology of nonfusogenic pathogen vacuoles. Annu Rev Microbiol 51 415 462
6. MorrissetteNSSibleyLD 2002 Cytoskeleton of apicomplexan parasites. Microbiol Mol Biol Rev 66 21 38
7. MartinAMLiuTLynnBCSinaiAP 2007 The Toxoplasma gondii parasitophorous vacuole membrane: transactions across the border. J Eukaryot Microbiol 54 25 28
8. MoudyRManningTJBeckersCJ 2001 The Loss of Cytoplasmic Potassium upon Host Cell Breakdown Triggers Egress of Toxoplasma gondii. J Biol Chem 276 41492 41501
9. MondragonRFrixioneE 1996 Ca(2+)-dependence of conoid extrusion in Toxoplasma gondii tachyzoites. J Eukaryot Microbiol 43 120 127
10. LovettJLMarchesiniNMorenoSNSibleyLD 2002 Toxoplasma gondii microneme secretion involves intracellular Ca(2+) release from inositol 1,4,5-triphosphate (IP(3))/ryanodine-sensitive stores. J Biol Chem 277 25870 25876
11. CarruthersVBSibleyLD 1997 Sequential protein secretion from three distinct organelles of Toxoplasma gondii accompanies invasion of human fibroblasts. Eur J Cell Biol 73 114 123
12. StommelEWElyKHSchwartzmanJDKasperLH 1997 Toxoplasma gondii: dithiol-induced Ca2+ flux causes egress of parasites from the parasitophorous vacuole. Exp Parasitol 87 88 97
13. HoffEFCarruthersVB 2002 Is Toxoplasma egress the first step in invasion? Trends Parasitol 18 251 255
14. CarruthersVBShermanGDSibleyLD 2000 The Toxoplasma adhesive protein MIC2 is proteolytically processed at multiple sites by two parasite-derived proteases. J Biol Chem 275 14346 14353
15. CarruthersVBSibleyLD 1999 Mobilization of intracellular calcium stimulates microneme discharge in Toxoplasma gondii. Mol Microbiol 31 421 428
16. KafsackBFCPenaJDOCoppensIRavindranSBoothroydJC 2009 Rapid membrane disruption by a perforin-like protein facilitates parasite exit from host cells. Science 323 530 533
17. DobrowolskiJMSibleyLD 1996 Toxoplasma invasion of mammalian cells is powered by the actin cytoskeleton of the parasite. Cell 84 933 939
18. RabenauKESohrabiATripathyAReitterCAjiokaJW 2001 TgM2AP participates in Toxoplasma gondii invasion of host cells and is tightly associated with the adhesive protein TgMIC2. Mol Microbiol 41 537 547
19. Herm-GotzAWeissSStratmannRFujita-BeckerSRuffC 2002 Toxoplasma gondii myosin A and its light chain: a fast, single-headed, plus-end-directed motor. Embo J 21 2149 2158
20. MeissnerMSchluterDSoldatiD 2002 Role of Toxoplasma gondii myosin A in powering parasite gliding and host cell invasion. Science 298 837 840
21. WetzelDMHakanssonSHuKRoosDSibleyLD 2003 Actin filament polymerization regulates gliding motility by apicomplexan parasites. Mol Biol Cell 14 396 406
22. JewettTJSibleyLD 2003 Aldolase forms a bridge between cell surface adhesins and the actin cytoskeleton in apicomplexan parasites. Mol Cell 11 885 894
23. GaskinsEGilkSDeVoreNMannTWardG 2004 Identification of the membrane receptor of a class XIV myosin in Toxoplasma gondii. J Cell Biol 165 383 393
24. HuynhM-HCarruthersVB 2006 Toxoplasma MIC2 is a major determinant of invasion and virulence. PLoS Pathog 2 e84
25. PomelSLukFCYBeckersCJM 2008 Host cell egress and invasion induce marked relocations of glycolytic enzymes in Toxoplasma gondii tachyzoites. PLoS Pathog 4 e1000188
26. HeaslipATLeungJMCareyKLCattiFWarshawDM 2010 A small-molecule inhibitor of T. gondii motility induces the posttranslational modification of myosin light chain-1 and inhibits myosin motor activity. PLoS Pathog 6 e1000720
27. FrenalKPolonaisVMarqJBStratmannRLimenitakisJ 2010 Functional dissection of the apicomplexan glideosome molecular architecture. Cell Host Microbe 8 343 357
28. KieschnickHWakefieldTNarducciCABeckersC 2001 Toxoplasma gondii attachment to host cells is regulated by a calmodulin- like domain protein kinase. J Biol Chem 276 12369 12377
29. WiersmaHIGaluskaSETomleyFMSibleyLDLiberatorPA 2004 A role for coccidian cGMP-dependent protein kinase in motility and invasion. Int J Parasitol 34 369 380
30. SugiTKatoKKobayashiKWatanabeSKurokawaH 2010 Use of the kinase inhibitor analog 1NM-PP1 reveals a role for Toxoplasma gondii CDPK1 in the invasion step. Eukaryot Cell 9 667 670
31. LouridoSShumanJZhangCShokatKMHuiR 2010 Calcium-dependent protein kinase 1 is an essential regulator of exocytosis in Toxoplasma. Nature 465 359 362
32. HuKJohnsonJFlorensLFraunholzMSuravajjalaS 2006 Cytoskeletal components of an invasion machine – the apical complex of Toxoplasma gondii. PLoS Pathog 2 0121 0139
33. DillonSCZhangXTrievelRCChengX 2005 The SET-domain protein superfamily: protein lysine methyltransferases. Genome Biol 6 227
34. ChengXCollinsREZhangX 2005 Structural and sequence motifs of protein (histone) methylation enzymes. Annu Rev Biophys Biomol Struct 34 267 294
35. Santos-RosaHSchneiderRBannisterAJSherriffJBernsteinBE 2002 Active genes are tri-methylated at K4 of histone H3. Nature 419 407 411
36. KroganNJKimMTongAGolshaniACagneyG 2003 Methylation of histone H3 by Set2 in Saccharomyces cerevisiae is linked to transcriptional elongation by RNA polymerase II. Mol Cell Biol 23 4207 4218
37. SchaftDRoguevAKotovicKMShevchenkoASarovM 2003 The histone 3 lysine 36 methyltransferase, SET2, is involved in transcriptional elongation. Nucleic Acids Res 31 2475 2482
38. BarskiACuddapahSCuiKRohT-YSchonesDE 2007 High-resolution profiling of histone methylations in the human genome. Cell 129 823 837
39. GissotMKellyKAAjiokaJWGreallyJMKimK 2007 Epigenomic modifications predict active promoters and gene structure in Toxoplasma gondii. PLoS Pathog 3 e77
40. HeintzmanNDHonGCHawkinsRDKheradpourPStarkA 2009 Histone modifications at human enhancers reflect global cell-type-specific gene expression. Nature 459 108 112
41. SautelCFCannellaDBastienOKiefferSAldebertD 2007 SET8-mediated methylations of histone H4 lysine 20 mark silent heterochromatic domains in apicomplexan genomes. Mol Cell Biol 27 5711 5724
42. SautelCFOrtetPSaksoukNKiefferSGarinJ 2009 The histone methylase KMTox interacts with the redox-sensor peroxiredoxin-1 and targets genes involved in Toxoplasma gondii antioxidant defences. Mol Microbiol 71 212 226
43. HuK 2008 Organizational Changes of the Daughter Basal Complex during the Parasite Replication of Toxoplasma gondii. PLoS Pathog 4 108 121
44. HuKRoosDSMurrayJM 2002 A novel polymer of tubulin forms the conoid of Toxoplasma gondii. J Cell Biol 156 1039 1050
45. GubbelsMVaishnavaSBootNDubremetzJFStriepenB 2006 A MORN-repeat protein is a dynamic component of the Toxoplasma gondii cell division apparatus. J Cell Sci 119 2236 2245
46. SauerBHendersonN 1988 Site-specific DNA recombination in mammalian cells by the Cre recombinase of bacteriophage P1. Proc Natl Acad Sci U S A 85 5166 5170
47. BrechtSErdhartHSoeteMSoldatiD 1999 Genome engineering of Toxoplasma gondii using the site-specific recombinase Cre. Gene 234 239 247
48. HeaslipATDzierszinskiFSteinBHuK 2010 TgMORN1 is a key organizer for the basal complex of Toxoplasma gondii. PLoS Pathog 6 e1000754
49. CareyKLWestwoodNJMitchisonTJWardGE 2004 A small-molecule approach to studying invasive mechanisms of Toxoplasma gondii. Proc Natl Acad Sci U S A 101 7433 7438
50. MitalJMeissnerMSoldatiDWardGE 2005 Conditional expression of Toxoplasma gondii apical membrane antigen-1 (TgAMA1) demonstrates that TgAMA1 plays a critical role in host cell invasion. Mol Biol Cell 16 4341 4349
51. van den HoffMJMoormanAFLamersWH 1992 Electroporation in ‘intracellular’ buffer increases cell survival. Nucleic Acids Res 20 2902
52. ChuikovSKurashJKWilsonJRXiaoBJustinN 2004 Regulation of p53 activity through lysine methylation. Nature 432 353 360
53. HuangJSenguptaREspejoABLeeMGDorseyJA 2007 p53 is regulated by the lysine demethylase LSD1. Nature 449 105 108
54. EaC-KBaltimoreD 2009 Regulation of NF-kappaB activity through lysine monomethylation of p65. Proc Natl Acad Sci U S A 106 18972 18977
55. VolkelPAngrandPO 2007 The control of histone lysine methylation in epigenetic regulation. Biochimie 89 1 20
56. Michaud-LevesqueJRichardS 2009 Thrombospondin-1 is a transcriptional repression target of PRMT6. J Biol Chem 284 21338 21346
57. XiaBJoubertAGrovesBVoKAshrafD 2010 Modulation of cell adhesion and migration by the histone methyltransferase subunit mDpy-30 and its interacting proteins. PloS One 5 e11771
58. BeckersCJRoosDSDonaldRGLuftBJSchwabJC 1995 Inhibition of cytoplasmic and organellar protein synthesis in Toxoplasma gondii. Implications for the target of macrolide antibiotics. J Clin Invest 95 367 376
59. LorestaniASheinerLYangKRobertsonSDSahooN 2010 A Toxoplasma MORN1 null mutant undergoes repeated divisions but is defective in basal assembly, apicoplast division and cytokinesis. PloS One 5 e12302
60. HuangJBergerSL 2008 The emerging field of dynamic lysine methylation of non-histone proteins. Curr Opin Genet Dev 18 152 158
61. YangX-DLambAChenL-F 2009 Methylation, a new epigenetic mark for protein stability. Epigenetics 4 429 433
62. ShawMKComptonHLRoosDSTilneyLG 2000 Microtubules, but not actin filaments, drive daughter cell budding and cell division in Toxoplasma gondii. J Cell Sci 113 1241 1254
63. RoosDSDonaldRGMorrissetteNSMoultonAL 1994 Molecular tools for genetic dissection of the protozoan parasite Toxoplasma gondii. Methods Cell Biol 45 27 78
64. DonaldRGKCarterDUllmanBRoosDS 1996 Insertional tagging, cloning, and expression of the Toxoplasma gondii hypoxanthine-xanthine-guanine phosphoribosyltransferase gene. Use as a selectable marker for stable transformation. J Biol Chem 271 14010 14019
65. HeaslipAEms-McClungSCHuK 2009 TgICMAP1 is a novel microtubule binding protein in Toxoplasma gondii. PloS One 4 e7406
66. SladewskiTEHetrickKMFosterPL 2011 Escherichia coli Rep DNA helicase and error-prone DNA polymerase IV interact physically and functionally. Mol Microbiol 80 524 541
67. BeckersCJDubremetzJFMercereau-PuijalonOJoinerKA 1994 The Toxoplasma gondii rhoptry protein ROP 2 is inserted into the parasitophorous vacuole membrane, surrounding the intracellular parasite, and is exposed to the host cell membrane. J Cell Biol 127 947 961
68. FingermanIDuHBriggsS 2008 In Vitro Histone Methyltransferase Assay. Cold Spring Harb Protoc doi:10.1101/pdb.prot4939
69. TanXRotllantJLiHDe DeynePDuSJ 2006 SmyD1, a histone methyltransferase, is required for myofibril organization and muscle contraction in zebrafish embryos. Proc Natl Acad Sci U S A 103 2713 2718
70. FicheraMEBhopaleMKRoosDS 1995 In vitro assays elucidate peculiar kinetics of clindamycin action against Toxoplasma gondii. Antimicrob Agents & Chemother 39 1530 1537
71. CarruthersVBGiddingsOKSibleyLD 1999 Secretion of micronemal proteins is associated with toxoplasma invasion of host cells. Cell Microbiol 1 225 235
72. HuynhMHRabenauKEHarperJMBeattyWLSibleyLD 2003 Rapid invasion of host cells by Toxoplasma requires secretion of the MIC2-M2AP adhesive protein complex. Embo J 22 2082 2090
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Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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