A leucine aminopeptidase is involved in kinetoplast DNA segregation in Trypanosoma brucei

. 2017 Apr ; 13 (4) : e1006310. [epub] 20170407

Jazyk angličtina Země Spojené státy americké Médium electronic-ecollection

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/pmid28388690

Grantová podpora
MR/P009018/1 Medical Research Council - United Kingdom
MR/N010558/1 Medical Research Council - United Kingdom
203134/Z/16/Z Wellcome Trust - United Kingdom
MR/K008749/1 Medical Research Council - United Kingdom
Wellcome Trust - United Kingdom

Odkazy

PubMed 28388690
PubMed Central PMC5397073
DOI 10.1371/journal.ppat.1006310
PII: PPATHOGENS-D-16-01055
Knihovny.cz E-zdroje

The kinetoplast (k), the uniquely packaged mitochondrial DNA of trypanosomatid protists is formed by a catenated network of minicircles and maxicircles that divide and segregate once each cell cycle. Although many proteins involved in kDNA replication and segregation are now known, several key steps in the replication mechanism remain uncharacterized at the molecular level, one of which is the nabelschnur or umbilicus, a prominent structure which in the mammalian parasite Trypanosoma brucei connects the daughter kDNA networks prior to their segregation. Here we characterize an M17 family leucyl aminopeptidase metalloprotease, termed TbLAP1, which specifically localizes to the kDNA disk and the nabelschur and represents the first described protein found in this structure. We show that TbLAP1 is required for correct segregation of kDNA, with knockdown resulting in delayed cytokinesis and ectopic expression leading to kDNA loss and decreased cell proliferation. We propose that TbLAP1 is required for efficient kDNA division and specifically participates in the separation of daughter kDNA networks.

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Jensen RE, Englund PT. Network News: The Replication of Kinetoplast DNA. Annu Rev Microbiol. 2012;66: 473–491. doi: 10.1146/annurev-micro-092611-150057 PubMed DOI

Ogbadoyi EO, Robinson DR, Gull K. A high-order trans-membrane structural linkage is responsible for mitochondrial genome positioning and segregation by flagellar basal bodies in trypanosomes. Mol Biol Cell. 2003; 14:1769–1779. doi: 10.1091/mbc.E02-08-0525 PubMed DOI PMC

Woodward R, Gull K. Timing of nuclear and kinetoplast DNA replication and early morphological events in the cell cycle of Trypanosoma brucei. J Cell Sci. 1990; 95:49–57. PubMed

Dean S, Gould MK, Dewar CE, Schnaufer AC. Single point mutations in ATP synthase compensate for mitochondrial genome loss in trypanosomes. Proc Natl Acad Sci USA. 2013; 110:14741–14746. doi: 10.1073/pnas.1305404110 PubMed DOI PMC

Roy Chowdhury A, Bakshi R, Wang J, Yildirir G, Liu B, Pappas-Brown V, et al. The killing of African trypanosomes by ethidium bromide. PLoS Pathog. 2010; 6:e1001226–14. doi: 10.1371/journal.ppat.1001226 PubMed DOI PMC

Shlomai J. The structure and replication of kinetoplast DNA. Curr Mol Med. 2004; 4:623–647. PubMed

Simpson L. The mitochondrial genome of kinetoplastid protozoa: genomic organization, transcription, replication, and evolution. Annu Rev Microbiol. 1987; 41:363–382. doi: 10.1146/annurev.mi.41.100187.002051 PubMed DOI

Aphasizhev R, Aphasizheva I. Mitochondrial RNA editing in trypanosomes: small RNAs in control. Biochimie. 2014; 100:125–131. doi: 10.1016/j.biochi.2014.01.003 PubMed DOI PMC

Verner Z, Basu S, Benz C, Dixit S, Dobáková E, Faktorová D, et al. Malleable Mitochondrion of Trypanosoma brucei. 2015; 315:73–151. doi: 10.1016/bs.ircmb.2014.11.001 PubMed DOI

Read LK, Lukeš J, Hashimi H. Trypanosome RNA editing: the complexity of getting U in and taking U out. WIREs RNA. 2015. PubMed PMC

Koslowsky D, Sun Y, Hindenach J, Theisen T, Lucas J. The insect-phase gRNA transcriptome in Trypanosoma brucei. Nucleic Acids Res. 2014; 42:1873–1886. doi: 10.1093/nar/gkt973 PubMed DOI PMC

Shapiro TA. Kinetoplast DNA maxicircles: networks within networks. Proc Natl Acad Sci USA. 1993; 90:7809–7813. PubMed PMC

Rauch CA, Pérez-Morga D, Cozzarelli NR, Englund PT. The absence of supercoiling in kinetoplast DNA minicircles. EMBO J. 1993; 12:403–411. PubMed PMC

Chen J, Rauch CA, White JH, Englund PT, Cozzarelli NR. The topology of the kinetoplast DNA network. Cell. 1995; 80:61–69. PubMed

Melendy T, Sheline C, Ray DS. Localization of a type II DNA topoisomerase to two sites at the periphery of the kinetoplast DNA of Crithidia fasciculata. Cell. 1988; 55:1083–1088. PubMed

Drew ME, Englund PT. Intramitochondrial location and dynamics of Crithidia fasciculata kinetoplast minicircle replication intermediates. J Cell Biol. 2001; 153:735–744. PubMed PMC

Kitchin PA, Klein VA, Fein BI, Englund PT. Gapped minicircles. A novel replication intermediate of kinetoplast DNA. J Biol Chem. 1984; 259:15532–15539. PubMed

Liu B, Wang J, Yildirir G, Englund PT. TbPIF5 is a Trypanosoma brucei mitochondrial DNA helicase involved in processing of minicircle Okazaki fragments. PLoS Pathog. 2009; 5:e1000589 doi: 10.1371/journal.ppat.1000589 PubMed DOI PMC

Klingbeil MM, Motyka SA, Englund PT. Multiple mitochondrial DNA polymerases in Trypanosoma brucei. Mol Cell. 2002; 10:175–186. PubMed

Bruhn DF, Sammartino MP, Klingbeil MM. Three mitochondrial DNA polymerases are essential for kinetoplast DNA replication and survival of bloodstream form Trypanosoma brucei. Eukaryot Cell. 2011; 10:734–743. doi: 10.1128/EC.05008-11 PubMed DOI PMC

Downey N, Hines JC, Sinha KM, Ray DS. Mitochondrial DNA ligases of Trypanosoma brucei. Eukaryot Cell. 2005; 4:765–774. doi: 10.1128/EC.4.4.765-774.2005 PubMed DOI PMC

Liu B, Yildirir G, Wang J, Tolun G, Griffith JD, Englund PT. TbPIF1, a Trypanosoma brucei mitochondrial DNA helicase, is essential for kinetoplast minicircle replication. J Biol Chem. 2010; 285:7056–7066. doi: 10.1074/jbc.M109.084038 PubMed DOI PMC

Pérez-Morga D, Englund PT. The structure of replicating kinetoplast DNA networks. J Cell Biol. 1993; 123:1069–1079. PubMed PMC

Ferguson ML, Torri AF, Pérez-Morga D, Ward DC, Englund PT. Kinetoplast DNA replication: mechanistic differences between Trypanosoma brucei and Crithidia fasciculata. J Cell Biol. 1994; 126:631–639. PubMed PMC

Guilbride DL, Englund PT. The replication mechanism of kinetoplast DNA networks in several trypanosomatid species. J Cell Sci. 1998; 111:675–679. PubMed

Pérez-Morga DL, Englund PT. The attachment of minicircles to kinetoplast DNA networks during replication. Cell. 1993; 74:703–711. PubMed

Liu B, Wang J, Yaffe N, Lindsay ME, Zhao Z, Zick A, et al. Trypanosomes have six mitochondrial DNA helicases with one controlling kinetoplast maxicircle replication. Mol Cell 2009; 35:490–501. doi: 10.1016/j.molcel.2009.07.004 PubMed DOI PMC

Gluenz E, Shaw MK, Gull K. Structural asymmetry and discrete nucleic acid subdomains in the Trypanosoma brucei kinetoplast. Mol Microbiol. 2007; 64:1529–1539. doi: 10.1111/j.1365-2958.2007.05749.x PubMed DOI PMC

Gluenz E, Povelones ML, Englund PT, Gull K. The kinetoplast duplication cycle in Trypanosoma brucei is orchestrated by cytoskeleton-mediated cell morphogenesis. Mol Cell Biol. 2011; 31:1012–1021. doi: 10.1128/MCB.01176-10 PubMed DOI PMC

Rawlings ND, Barrett AJ. Introduction: Metallopeptidases and Their Clans. Handbook of Proteolytic Enzymes. 2012. pp. 325–370.

Byrd CM, Bolken TC. Leucyl Aminopeptidase (Animal). Handbook of Proteolytic Enzymes. 2012. pp. 1465–1470.

Narváez-Vásquez J, Tu C-J, Park S-Y, Walling LL. Targeting and localization of wound-inducible leucine aminopeptidase A in tomato leaves. Planta. 2008; 227:341–351. doi: 10.1007/s00425-007-0621-0 PubMed DOI

Jarocki VM, Santos J, Tacchi JL, Raymond BBA, Deutscher AT, Jenkins C, et al. MHJ_0461 is a multifunctional leucine aminopeptidase on the surface of Mycoplasma hyopneumoniae. Open Biol. 2015; 5:140175–140175. doi: 10.1098/rsob.140175 PubMed DOI PMC

Deng C, Sun J, Li X, Wang L, Hu X, Wang X, et al. Molecular identification and characterization of leucine aminopeptidase 2, an excretory-secretory product of Clonorchis sinensis. Mol Biol Rep. 2012; 39:9817–9826. doi: 10.1007/s11033-012-1848-9 PubMed DOI

Charlier D, Kholti A, Huysveld N, Gigot D, Maes D, Thia-Toong TL, et al. Mutational analysis of Escherichia coli PepA, a multifunctional DNA-binding aminopeptidase. J Mol Biol. 2000; 302:411–426. doi: 10.1006/jmbi.2000.4067 PubMed DOI

Ishizaki T, Tosaka A, Nara T, Aoshima N, Namekawa S, Watanabe K, et al. Leucine aminopeptidase during meiotic development. Eur J Biochem. 2002; 269:826–832. PubMed

Carroll RK, Robison TM, Rivera FE, Davenport JE, Jonsson I- M, Florczyk D, et al. Identification of an intracellular M17 family leucine aminopeptidase that is required for virulence in Staphylococcus aureus. Microbes Infect. 2012; 14:989–999. doi: 10.1016/j.micinf.2012.04.013 PubMed DOI PMC

Morty RE, Morehead J. Cloning and characterization of a leucyl aminopeptidase from three pathogenic Leishmania species. J Biol Chem. 2002; 277:26057–26065. doi: 10.1074/jbc.M202779200 PubMed DOI

Lee Y-R, Na B-K, Moon E-K, Song S-M, Joo S-Y, Kong H-H, et al. Essential role for an M17 leucine aminopeptidase in encystation of Acanthamoeba castellanii. PLoS ONE. 2015; 10:e0129884 doi: 10.1371/journal.pone.0129884 PubMed DOI PMC

Fowler JH, Narváez-Vásquez J, Aromdee DN, Pautot V, Holzer FM, Walling LL. Leucine aminopeptidase regulates defense and wound signaling in tomato downstream of jasmonic acid. Plant Cell. 2009; 21:1239–1251. doi: 10.1105/tpc.108.065029 PubMed DOI PMC

Scranton MA, Yee A, Park S-Y, Walling LL. Plant leucine aminopeptidases moonlight as molecular chaperones to alleviate stress-induced damage. J Biol Chem. 2012; 287:18408–18417. doi: 10.1074/jbc.M111.309500 PubMed DOI PMC

Chu L, Lai Y, Xu X, Eddy S, Yang S, Song L, et al. A 52-kDa leucyl aminopeptidase from Treponema denticola is a cysteinylglycinase that mediates the second step of glutathione metabolism. J Biol Chem. 2008; 283:19351–19358. doi: 10.1074/jbc.M801034200 PubMed DOI PMC

Nakai K, Horton P. PSORT: a program for detecting sorting signals in proteins and predicting their subcellular localization. Trends Biochem Sci. 1999; 24:34–36. PubMed

Bannai H, Tamada Y, Maruyama O, Nakai K, Miyano S. Extensive feature detection of N-terminal protein sorting signals. Bioinformatics. 2002; 18:298–305. PubMed

Claros MG, Vincens P. Computational method to predict mitochondrially imported proteins and their targeting sequences. Eur J Biochem. 1996; 241: 779–786. PubMed

Emanuelsson O, Brunak S, Heijne von G, Nielsen H. Locating proteins in the cell using TargetP, SignalP and related tools. Nat Protoc. 2007; 2:953–971. doi: 10.1038/nprot.2007.131 PubMed DOI

Robinson DR, Gull K. Basal body movements as a mechanism for mitochondrial genome segregation in the trypanosome cell cycle. Nature. 1991; 352:731–733. doi: 10.1038/352731a0 PubMed DOI

Ripley BD. Modelling spatial patterns. J R Stat Soc Series B Stat Methodol. 1977;39: 172–212.

Lagache T, Lang G, Sauvonnet N, Olivo-Marin J-C. Analysis of the spatial organization of molecules with robust statistics. PLoS ONE. 2013; 8:e80914–7. doi: 10.1371/journal.pone.0080914 PubMed DOI PMC

Týč J, Klingbeil MM, Lukeš J. Mitochondrial heat shock protein machinery hsp70/hsp40 is indispensable for proper mitochondrial DNA maintenance and replication. mBio. 2015;6: e02425–14. doi: 10.1128/mBio.02425-14 PubMed DOI PMC

Concepción-Acevedo J, Luo J, Klingbeil MM. Dynamic localization of Trypanosoma brucei mitochondrial DNA polymerase ID. Eukaryot Cell. 2012; 11:844–855. doi: 10.1128/EC.05291-11 PubMed DOI PMC

Povelones ML. Beyond replication: division and segregation of mitochondrial DNA in kinetoplastids. Mol Biochem Parasitol. 2014; 196:53–60. doi: 10.1016/j.molbiopara.2014.03.008 PubMed DOI

Cadavid-Restrepo G, Gastardelo TS, Faudry E, de Almeida H, Bastos IMD, Negreiros RS, et al. The major leucyl aminopeptidase of Trypanosoma cruzi (LAPTc) assembles into a homohexamer and belongs to the M17 family of metallopeptidases. BMC Biochem. 2011; 12:46 doi: 10.1186/1471-2091-12-46 PubMed DOI PMC

Benz C, Clucas C, Mottram JC, Hammarton TC. Cytokinesis in bloodstream stage Trypanosoma brucei requires a family of katanins and spastin. PLoS ONE. 2012; 7:e30367–12. doi: 10.1371/journal.pone.0030367 PubMed DOI PMC

Motyka SA, Drew ME, Yildirir G, Englund PT. Overexpression of a cytochrome b5 reductase-like protein causes kinetoplast DNA loss in Trypanosoma brucei. J Biol Chem. 2006; 281:18499–18506. doi: 10.1074/jbc.M602880200 PubMed DOI

Zhao Z, Lindsay ME, Roy Chowdhury A, Robinson DR, Englund PT. p166, a link between the trypanosome mitochondrial DNA and flagellum, mediates genome segregation. EMBO J. 2008; 27:143–154. doi: 10.1038/sj.emboj.7601956 PubMed DOI PMC

Wang J, Englund PT, Jensen RE. TbPIF8, a Trypanosoma brucei protein related to the yeast Pif1 helicase, is essential for cell viability and mitochondrial genome maintenance. Mol Microbiol. 2012; 83:471–485. doi: 10.1111/j.1365-2958.2011.07938.x PubMed DOI PMC

Beck K, Acestor N, Schulfer A, Anupama A, Carnes J, Panigrahi AK, et al. Trypanosoma brucei Tb927.2.6100 is an essential protein associated with kinetoplast DNA. Eukaryot Cell. 2013; 12:970–978. doi: 10.1128/EC.00352-12 PubMed DOI PMC

Hines JC, Ray DS. A second mitochondrial DNA primase is essential for cell growth and kinetoplast minicircle DNA replication in Trypanosoma brucei. Eukaryot Cell. 2011; 10:445–454. doi: 10.1128/EC.00308-10 PubMed DOI PMC

Lacomble S, Vaughan S, Gadelha C, Morphew MK, Shaw MK, McIntosh JR, et al. Basal body movements orchestrate membrane organelle division and cell morphogenesis in Trypanosoma brucei. J Cell Sci. 2010; 123:2884–2891. doi: 10.1242/jcs.074161 PubMed DOI PMC

Ploubidou A, Robinson DR, Docherty RC, Ogbadoyi EO, Gull K. Evidence for novel cell cycle checkpoints in trypanosomes: kinetoplast segregation and cytokinesis in the absence of mitosis. J Cell Sci. 1999; 112:4641–4650. PubMed

Colloms SD, Bath J, Sherratt DJ. Topological selectivity in Xer site-specific recombination. Cell. 1997; 88:855–864. PubMed

Strater N, Sherratt DJ, Colloms SD. X-ray structure of aminopeptidase A from Escherichia coli and a model for the nucleoprotein complex in Xer site-specific recombination. EMBO J. 1999; 18:4513–4522. doi: 10.1093/emboj/18.16.4513 PubMed DOI PMC

McCulloch R, Burke ME, Sherratt DJ. Peptidase activity of Escherichia coli aminopeptidase A is not required for its role in Xer site-specific recombination. Mol Microbiol. 1994; 12:241–251. PubMed

Reijns M, Lu Y, Leach S, Colloms SD. Mutagenesis of PepA suggests a new model for the Xer/cer synaptic complex. Mol Microbiol. 2005; 57:927–941. doi: 10.1111/j.1365-2958.2005.04716.x PubMed DOI

Zhang S, Yang X, Shi H, Li M, Xue Q, Ren H, et al. Overexpression of leucine aminopeptidase 3 contributes to malignant development of human esophageal squamous cell carcinoma. J Mol Histol. 2014; 45:283–292. doi: 10.1007/s10735-014-9566-3 PubMed DOI

Cappiello M, Lazzarotti A, Buono F, Scaloni A, D'Ambrosio C, Amodeo P, et al. New role for leucyl aminopeptidase in glutathione turnover. Biochem J. 2004; 378:35–44. doi: 10.1042/BJ20031336 PubMed DOI PMC

Vincent IM, Creek DJ, Burgess K, Woods DJ, Burchmore RJS, Barrett MP. Untargeted metabolomics reveals a lack of synergy between nifurtimox and eflornithine against Trypanosoma brucei. PLoS Negl Trop Dis. 2012; 6:e1618 doi: 10.1371/journal.pntd.0001618 PubMed DOI PMC

Edgar RC. MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 2004; 32:1792–1797. doi: 10.1093/nar/gkh340 PubMed DOI PMC

Castresana J. Selection of conserved blocks from multiple alignments for their use in phylogenetic analysis. Mol Biol Evol. 2000;17:540–552. PubMed

Gouy M, Guindon S, Gascuel O. SeaView version 4: A multiplatform graphical user interface for sequence alignment and phylogenetic tree building. Mol Biol Evol. 2010; 27:221–224. doi: 10.1093/molbev/msp259 PubMed DOI

Stamatakis A. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics. 2014; 30:1312–1313. doi: 10.1093/bioinformatics/btu033 PubMed DOI PMC

Wickstead B, Ersfeld K, Gull K. Targeting of a tetracycline-inducible expression system to the transcriptionally silent minichromosomes of Trypanosoma brucei. Mol Biochem Parasitol. 2002; 125:211–216. PubMed

Poon SK, Peacock L, Gibson W, Gull K, Kelly S. A modular and optimized single marker system for generating Trypanosoma brucei cell lines expressing T7 RNA polymerase and the tetracycline repressor. Open Biol. 2012; 2. PubMed PMC

Kelly S, Reed J, Kramer S, Ellis L, Webb H, Sunter J, et al. Functional genomics in Trypanosoma brucei: a collection of vectors for the expression of tagged proteins from endogenous and ectopic gene loci. Mol Biochem Parasitol. 2007; 154:103–109. doi: 10.1016/j.molbiopara.2007.03.012 PubMed DOI PMC

Oberholzer M, Morand S, Kunz S, Seebeck T. A vector series for rapid PCR-mediated c-terminal in situ tagging of Trypanosoma brucei genes. Mol Biochem Parasitol. 2006;145: 117–120. doi: 10.1016/j.molbiopara.2005.09.002 PubMed DOI

Dean S, Sunter J, Wheeler RJ, Hodkinson I, Gluenz E, Gull K. A toolkit enabling efficient, scalable and reproducible gene tagging in trypanosomatids. Open Biol. 2015; 5:140197–140197. doi: 10.1098/rsob.140197 PubMed DOI PMC

Alibu VP, Storm L, Haile S, Clayton C, Horn D. A doubly inducible system for RNA interference and rapid RNAi plasmid construction in Trypanosoma brucei. Mol Biochem Parasitol. 2005; 139: 75–82. doi: 10.1016/j.molbiopara.2004.10.002 PubMed DOI

Vondrušková E, van den Burg J, Zíková A, Ernst NL, Stuart K, Benne R, et al. RNA interference analyses suggest a transcript-specific regulatory role for mitochondrial RNA-binding proteins MRP1 and MRP2 in RNA editing and other RNA processing in Trypanosoma brucei. J Biol Chem. 2005; 280:2429–2438. doi: 10.1074/jbc.M405933200 PubMed DOI

Colasante C, Peña Diaz P, Clayton C, Voncken F. Mitochondrial carrier family inventory of Trypanosoma brucei brucei: Identification, expression and subcellular localisation. Mol Biochem Parasitol. 2009; 167:104–117. doi: 10.1016/j.molbiopara.2009.05.004 PubMed DOI

Sunter JD, Benz C, Andre J, Whipple S, McKean PG, Gull K, et al. Modulation of flagellum attachment zone protein FLAM3 and regulation of the cell shape in Trypanosoma brucei life cycle transitions. J Cell Sci. 2015; 128:3117–3130. doi: 10.1242/jcs.171645 PubMed DOI PMC

Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012; 9:671–675. PubMed PMC

Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012; 9:676–682. doi: 10.1038/nmeth.2019 PubMed DOI PMC

Hashimi H, McDonald L, Stríbrná E, Lukeš J. Trypanosome Letm1 protein is essential for mitochondrial potassium homeostasis. J Biol Chem. 2013; 288: 26914–26925. doi: 10.1074/jbc.M113.495119 PubMed DOI PMC

Bessat M, Ersfeld K. Functional characterization of cohesin SMC3 and separase and their roles in the segregation of large and minichromosomes in Trypanosoma brucei. Mol Microbiol. 2009; 71:1371–1385. doi: 10.1111/j.1365-2958.2009.06611.x PubMed DOI

Hashimi H, Zíková A, Panigrahi AK, Stuart KD, Lukeš J. TbRGG1, an essential protein involved in kinetoplastid RNA metabolism that is associated with a novel multiprotein complex. RNA. 2008;14: 970–980. doi: 10.1261/rna.888808 PubMed DOI PMC

Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001;29. PubMed PMC

Carnes J, Trotter JR, Ernst NL, Steinberg A, Stuart K. An essential RNase III insertion editing endonuclease in Trypanosoma brucei. Proc Natl Acad Sci USA. 2005; 102:16614–16619. doi: 10.1073/pnas.0506133102 PubMed DOI PMC

Ramakers C, Ruijter JM, Deprez RHL, Moorman AFM. Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) data. Neurosci Lett. 2003; 339:62–66. PubMed

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