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Proteomics and the Trypanosoma brucei cytoskeleton: advances and opportunities

Published online by Cambridge University Press:  04 April 2012

NEIL PORTMAN  and
KEITH GULL
NEIL PORTMAN
Affiliation:
The Sir William Dunn School of Pathology and Oxford Centre for Integrative Systems Biology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK
KEITH GULL*
Affiliation:
The Sir William Dunn School of Pathology and Oxford Centre for Integrative Systems Biology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK
*
*Author for correspondence: Professor Keith Gull, The Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK. Tel.: +44 (0)1865285455. E-mail: [email protected]
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Summary

Trypanosoma brucei is the etiological agent of devastating parasitic disease in humans and livestock in sub-saharan Africa. The pathogenicity and growth of the parasite are intimately linked to its shape and form. This is in turn derived from a highly ordered microtubule cytoskeleton that forms a tightly arrayed cage directly beneath the pellicular membrane and numerous other cytoskeletal structures such as the flagellum. The parasite undergoes extreme changes in cellular morphology during its life cycle and cell cycles which require a high level of integration and coordination of cytoskeletal processes. In this review we will discuss the role that proteomics techniques have had in advancing our understanding of the molecular composition of the cytoskeleton and its functions. We then consider future opportunities for the application of these techniques in terms of addressing some of the unanswered questions of trypanosome cytoskeletal cell biology with particular focus on the differences in the composition and organisation of the cytoskeleton through the trypanosome life-cycle.

Keywords

Trypanosoma bruceicytoskeletonproteomicflagellumflagella connectorBilobePFR
Type
Research Article
Information
Parasitology , Volume 139 , Issue 9: Symposia of the British Society for Parasitology Volume 48 Proteomic insights into parasite biology , August 2012 , pp. 1168 - 1177
Copyright
Copyright © Cambridge University Press 2012

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References

REFERENCES

Absalon, S., Blisnick, T., Kohl, L., Toutirais, G., Dore, G., Julkowska, D., Tavenet, A. and Bastin, P. (2008). Intraflagellar transport and functional analysis of genes required for flagellum formation in trypanosomes. Molecular Biology of the Cell 19, 929–944.CrossRefGoogle ScholarPubMed
Absalon, S., Kohl, L., Branche, C., Blisnick, T., Toutirais, G., Rusconi, F., Cosson, J., Bonhivers, M., Robinson, D. and Bastin, P. (2007). Basal body positioning is controlled by flagellum formation in Trypanosoma brucei. PLoS ONE 2(5), e437.CrossRefGoogle ScholarPubMed
Barry, J. D. and McCulloch, R. (2001). Antigenic variation in trypanosomes: enhanced phenotypic variation in a eukaryotic parasite. Advances in Parasitology 49, 1–70.Google Scholar
Bastin, P., Matthews, K. R. and Gull, K. (1996). The paraflagellar rod of 1kinetoplastida: solved and unsolved questions. Parasitology Today 12, 302–307.CrossRefGoogle ScholarPubMed
Bastin, P., Sherwin, T. and Gull, K. (1998). Paraflagellar rod is vital for trypanosome motility. Nature 391, 548.CrossRefGoogle Scholar
Berriman, M., Ghedin, E., Hertz-Fowler, C., Blandin, G., Renauld, H., Bartholomeu, D. C., Lennard, N. J., Caler, E., Hamlin, N. E., Haas, B., Bohme, U., Hannick, L., Aslett, M. A., Shallom, J., Marcello, L., Hou, L., Wickstead, B., Alsmark, U. C., Arrowsmith, C., Atkin, R. J., Barron, A. J., Bringaud, F., Brooks, K., Carrington, M., Cherevach, I., Chillingworth, T. J., Churcher, C., Clark, L. N., Corton, C. H., Cronin, A., Davies, R. M., Doggett, J., Djikeng, A., Feldblyum, T., Field, M. C., Fraser, A., Goodhead, I., Hance, Z., Harper, D., Harris, B. R., Hauser, H., Hostetler, J., Ivens, A., Jagels, K., Johnson, D., Johnson, J., Jones, K., Kerhornou, A. X., Koo, H., Larke, N., Landfear, S., Larkin, C., Leech, V., Line, A., Lord, A., Macleod, A., Mooney, P. J., Moule, S., Martin, D. M., Morgan, G. W., Mungall, K., Norbertczak, H., Ormond, D., Pai, G., Peacock, C. S., Peterson, J., Quail, M. A., Rabbinowitsch, E., Rajandream, M. A., Reitter, C., Salzberg, S. L., Sanders, M., Schobel, S., Sharp, S., Simmonds, M., Simpson, A. J., Tallon, L., Turner, C. M., Tait, A., Tivey, A. R., Van Aken, S., Walker, D., Wanless, D., Wang, S., White, B., White, O., Whitehead, S., Woodward, J., Wortman, J., Adams, M. D., Embley, T. M., Gull, K., Ullu, E., Barry, J. D., Fairlamb, A. H., Opperdoes, F., Barrell, B. G., Donelson, J. E., Hall, N., Fraser, C. M., and et al. (2005). The genome of the African trypanosome Trypanosoma brucei. Science 309, 416–422.CrossRefGoogle ScholarPubMed
Bonhivers, M., Nowacki, S., Landrein, N. and Robinson, D. R. (2008). Biogenesis of the trypanosome endo-exocytotic organelle is cytoskeleton mediated. PLoS Biology 6(5), e105.CrossRefGoogle ScholarPubMed
Brems, S., Guilbride, D. L., Gundlesdodjir-Planck, D., Busold, C., Luu, V. D., Schanne, M., Hoheisel, J. and Clayton, C. (2005). The transcriptomes of Trypanosoma brucei Lister 427 and TREU927 bloodstream and procyclic trypomastigotes. Molecular and Biochemical Parasitology 139, 163–172.CrossRefGoogle ScholarPubMed
Briggs, L. J., McKean, P. G., Baines, A., Moreira-Leite, F., Davidge, J., Vaughan, S. and Gull, K. (2004). The flagella connector of Trypanosoma brucei: an unusual mobile transmembrane junction. Journal of Cell Science 117, 1641–1651.CrossRefGoogle ScholarPubMed
Broadhead, R., Dawe, H. R., Farr, H., Griffiths, S., Hart, S. R., Portman, N., Shaw, M. K., Ginger, M. L., Gaskell, S. J., McKean, P. G. and Gull, K. (2006). Flagellar motility is required for the viability of the bloodstream trypanosome. Nature 440, 224–227.CrossRefGoogle ScholarPubMed
Davidge, J. A., Chambers, E., Dickinson, H. A., Towers, K., Ginger, M. L., McKean, P. G. and Gull, K. (2006). Trypanosome IFT mutants provide insight into the motor location for mobility of the flagella connector and flagellar membrane formation. Journal of Cell Science 119, 3935–3943.CrossRefGoogle ScholarPubMed
Fenn, K. and Matthews, K. R. (2007). The cell biology of Trypanosoma brucei differentiation. Current Opinions in Microbiology 10, 539–546.CrossRefGoogle ScholarPubMed
Gadelha, C., Wickstead, B., de Souza, W., Gull, K. and Cunha-e-Silva, N. (2005). Cryptic paraflagellar rod in endosymbiont-containing kinetoplastid protozoa. Eukaryotic Cell 4, 516–525.CrossRefGoogle Scholar
Gull, K. (1999). The cytoskeleton of trypanosomatid parasites. Annual Review of Microbiology 53, 629–655.CrossRefGoogle ScholarPubMed
He, C. Y., Pypaert, M. and Warren, G. (2005). Golgi duplication in Trypanosoma brucei requires Centrin2. Science 310, 1196–1198.CrossRefGoogle ScholarPubMed
Henley, G. L., Lee, C. M. and Takeuchi, A. (1978). Electron microscopy observations on Trypanosoma brucei: freeze-cleaving and thin-sectioning study of the apical part of the flagellar pocket. Zeitschrift für Parasitenkunde 55, 181–187.CrossRefGoogle ScholarPubMed
Hertz-Fowler, C., Ersfeld, K. and Gull, K. (2001). CAP5.5, a life-cycle-regulated, cytoskeleton-associated protein is a member of a novel family of calpain-related proteins in Trypanosoma brucei. Molecular and Biochemical Parasitology 116, 25–34.CrossRefGoogle ScholarPubMed
Hirokawa, N., Tanaka, Y., Okada, Y. and Takeda, S. (2006). Nodal flow and the generation of left-right asymmetry. Cell 125, 33–45.CrossRefGoogle ScholarPubMed
Horn, D. and McCulloch, R. (2010). Molecular mechanisms underlying the control of antigenic variation in African trypanosomes. Current Opinion in Microbiology 13, 700–705.CrossRefGoogle ScholarPubMed
Hyams, J. S. (1982). The Euglena paraflagellar rod: structure, relationship to other flagellar components and preliminary biochemical characterization. Journal of Cell Science 55, 199–210.CrossRefGoogle ScholarPubMed
Jensen, B. C., Sivam, D., Kifer, C. T., Myler, P. J. and Parsons, M. (2009). Widespread variation in transcript abundance within and across developmental stages of Trypanosoma brucei. BMC Genomics 10, 482.CrossRefGoogle ScholarPubMed
Kabani, S., Fenn, K., Ross, A., Ivens, A., Smith, T. K., Ghazal, P. and Matthews, K. (2009). Genome-wide expression profiling of in vivo-derived bloodstream parasite stages and dynamic analysis of mRNA alterations during synchronous differentiation in Trypanosoma brucei. BMC Genomics 10, 427.CrossRefGoogle ScholarPubMed
Koumandou, V. L., Natesan, S. K., Sergeenko, T. and Field, M. C. (2008). The trypanosome transcriptome is remodelled during differentiation but displays limited responsiveness within life stages. BMC Genomics 9, 298.CrossRefGoogle ScholarPubMed
Kozminski, K. G., Johnson, K. A., Forscher, P. and Rosenbaum, J. L. (1993). A motility in the eukaryotic flagellum unrelated to flagellar beating. Proceedings of the National Academy of Sciences, USA 90, 5519–5523.CrossRefGoogle ScholarPubMed
Lacomble, S., Portman, N. and Gull, K. (2009 a). A protein-protein interaction map of the Trypanosoma brucei paraflagellar rod. PLoS One 4(11), e7685.CrossRefGoogle ScholarPubMed
Lacomble, S., Vaughan, S., Gadelha, C., Morphew, M. K., Shaw, M. K., McIntosh, J. R. and Gull, K. (2009 b). Three-dimensional cellular architecture of the flagellar pocket and associated cytoskeleton in trypanosomes revealed by electron microscope tomography. Journal of Cell Science 122, 1081–1090.CrossRefGoogle ScholarPubMed
LaCount, D. J., Barrett, B. and Donelson, J. E. (2002). Trypanosoma brucei FLA1 is required for flagellum attachment and cytokinesis. Journal of Biological Chemistry 277, 17580–17588.CrossRefGoogle ScholarPubMed
Landfear, S. M. and Ignatushchenko, M. (2001). The flagellum and flagellar pocket of trypanosomatids. Molecular and Biochemical Parasitology 115, 1–17.CrossRefGoogle ScholarPubMed
Liu, Q., Tan, G., Levenkova, N., Li, T., Pugh, E. N., Rux, J. J., Speicher, D. W. and Pierce, E. A. (2007). The proteome of the mouse photoreceptor sensory cilium complex. Molecular and Cellular Proteomics 6, 1299–1317.CrossRefGoogle ScholarPubMed
Matthews, K. R. and Gull, K. (1994). Evidence for an interplay between cell cycle progression and the initiation of differentiation between life cycle forms of African trypanosomes. Journal of Cell Biololgy 125, 1147–1156.CrossRefGoogle ScholarPubMed
McGhee, R. B. and Cosgrove, W. B. (1980). Biology and physiology of the lower Trypanosomatidae. Microbiological Reviews 44, 140–173.CrossRefGoogle ScholarPubMed
Moreira-Leite, F. F., Sherwin, T., Kohl, L. and Gull, K. (2001). A trypanosome structure involved in transmitting cytoplasmic information during cell division. Science 294, 610–612.CrossRefGoogle ScholarPubMed
Morriswood, B., He, C. Y., Sealey-Cardona, M., Yelinek, J., Pypaert, M. and Warren, G. (2009). The bilobe structure of Trypanosoma brucei contains a MORN-repeat protein. Molecular and Biochemical Parasitology 167, 95–103.CrossRefGoogle ScholarPubMed
Nozaki, T., Haynes, P. A. and Cross, G. A. (1996). Characterization of the Trypanosoma brucei homologue of a Trypanosoma cruzi flagellum-adhesion glycoprotein. Molecular and Biochemical Parasitology 82, 245–255.CrossRefGoogle ScholarPubMed
Oberholzer, M., Langousis, G., Nguyen, H. T., Saada, E. A., Shimogawa, M. M., Jonsson, Z. O., Nguyen, S. M., Wohlschlegel, J. A. and Hill, K. L. (2011). Independent analysis of the flagellum surface and matrix proteomes provides insight into flagellum signaling in mammalian-infectious Trypanosoma brucei. Molecular and Cellular Proteomics 10, M111.010538.CrossRefGoogle ScholarPubMed
Ogbadoyi, E. O., Robinson, D. R. and Gull, K. (2003). A high-order trans-membrane structural linkage is responsible for mitochondrial genome positioning and segregation by flagellar basal bodies in trypanosomes. Molecular Biology of the Cell 14, 1769–1779.CrossRefGoogle ScholarPubMed
Olego-Fernandez, S., Vaughan, S., Shaw, M. K., Gull, K. and Ginger, M. L. (2009). Cell morphogenesis of Trypanosoma brucei requires the paralogous, differentially expressed calpain-related proteins CAP5.5 and CAP5.5 V. Protist 160, 576–590.CrossRefGoogle Scholar
Ono, Y. and Sorimachi, H. (2012). Calpains - An elaborate proteolytic system. Biochimica et Biophysica Acta 1824, 224–236.CrossRefGoogle ScholarPubMed
Ostrowski, L. E., Blackburn, K., Radde, K. M., Moyer, M. B., Schlatzer, D. M., Moseley, A. and Boucher, R. C. (2002). A proteomic analysis of human cilia: identification of novel components. Molecular and Cellular Proteomics 1, 451–465.CrossRefGoogle ScholarPubMed
Pazour, G. J., Agrin, N., Leszyk, J. and Witman, G. B. (2005). Proteomic analysis of a eukaryotic cilium. Journal of Cell Biology 170, 103–113.CrossRefGoogle ScholarPubMed
Portman, N. and Gull, K. (2010). The paraflagellar rod of kinetoplastid parasites: from structure to components and function. International Journal for Parasitology 40, 135–148.CrossRefGoogle ScholarPubMed
Portman, N., Lacomble, S., Thomas, B., McKean, P. G. and Gull, K. (2009). Combining RNA interference mutants and comparative proteomics to identify protein components and dependences in a eukaryotic flagellum. Journal of Biological Chemistry 284, 5610–5619.CrossRefGoogle Scholar
Pullen, T. J., Ginger, M. L., Gaskell, S. J. and Gull, K. (2004). Protein targeting of an unusual, evolutionarily conserved adenylate kinase to a eukaryotic flagellum. Molecular Biology of the Cell 15, 3257–3265.CrossRefGoogle ScholarPubMed
Robinson, D. R. and Gull, K. (1991). Basal body movements as a mechanism for mitochondrial genome segregation in the trypanosome cell cycle. Nature 352, 731–733.CrossRefGoogle ScholarPubMed
Robinson, D. R., Sherwin, T., Ploubidou, A., Byard, E. H. and Gull, K. (1995). Microtubule polarity and dynamics in the control of organelle positioning, segregation, and cytokinesis in the trypanosome cell cycle. Journal of Cell Biology 128, 1163–1172.CrossRefGoogle ScholarPubMed
Rotureau, B., Subota, I. and Bastin, P. (2011). Molecular bases of cytoskeleton plasticity during the Trypanosoma brucei parasite cycle. Cellular Microbiology 13, 705–716.CrossRefGoogle ScholarPubMed
Russell, D. G., Newsam, R. J., Palmer, G. C. and Gull, K. (1983). Structural and biochemical characterisation of the paraflagellar rod of Crithidia fasciculata. European Journal of Cell Biology 30, 137–143.Google ScholarPubMed
Santrich, C., Moore, L., Sherwin, T., Bastin, P., Brokaw, C., Gull, K. and LeBowitz, J. H. (1997). A motility function for the paraflagellar rod of Leishmania parasites revealed by PFR-2 gene knockouts. Molecular and Biochemical Parasitology 90, 95–109.CrossRefGoogle ScholarPubMed
Sharma, R., Gluenz, E., Peacock, L., Gibson, W., Gull, K. and Carrington, M. (2009). The heart of darkness: growth and form of Trypanosoma brucei in the tsetse fly. Trends in Parasitology 25, 517–524.CrossRefGoogle ScholarPubMed
Sharma, R., Peacock, L., Gluenz, E., Gull, K., Gibson, W. and Carrington, M. (2008). Asymmetric cell division as a route to reduction in cell length and change in cell morphology in trypanosomes. Protist 159, 137–151.CrossRefGoogle ScholarPubMed
Sherwin, T. and Gull, K. (1989). The cell division cycle of Trypanosoma brucei brucei: timing of event markers and cytoskeletal modulations. Philosophical Transactions of the Royal Society B: Biological Sciences 323, 573–588.Google ScholarPubMed
Siegel, T. N., Hekstra, D. R., Wang, X., Dewell, S. and Cross, G. A. (2010). Genome-wide analysis of mRNA abundance in two life-cycle stages of Trypanosoma brucei and identification of splicing and polyadenylation sites. Nucleic Acids Research 38, 4946–4957.CrossRefGoogle ScholarPubMed
Smith, J. C., Northey, J. G., Garg, J., Pearlman, R. E. and Siu, K. W. (2005). Robust method for proteome analysis by MS/MS using an entire translated genome: demonstration on the ciliome of Tetrahymena thermophila. Journal of Proteome Research 4, 909–919.CrossRefGoogle ScholarPubMed
Taylor, J. E. and Rudenko, G. (2006). Switching trypanosome coats: what's in the wardrobe? Trends in Genetics 22, 614–620.CrossRefGoogle ScholarPubMed
Tetley, L. and Vickerman, K. (1985). Differentiation in Trypanosoma brucei: host-parasite cell junctions and their persistence during acquisition of the variable antigen coat. Journal of Cell Science 74, 1–19.CrossRefGoogle ScholarPubMed
Vaughan, S., Kohl, L., Ngai, I., Wheeler, R. J. and Gull, K. (2008). A repetitive protein essential for the flagellum attachment zone filament structure and function in Trypanosoma brucei. Protist 159, 127–136.CrossRefGoogle ScholarPubMed
Vedrenne, C., Giroud, C., Robinson, D. R., Besteiro, S., Bosc, C., Bringaud, F. and Baltz, T. (2002). Two related subpellicular cytoskeleton-associated proteins in Trypanosoma brucei stabilize microtubules. Molecular Biology of the Cell 13, 1058–1070.CrossRefGoogle ScholarPubMed
Vickerman, K. (1969). On the surface coat and flagellar adhesion in trypanosomes. Journal of Cell Science 5, 163–193.CrossRefGoogle ScholarPubMed
Vickerman, K. (1985). Developmental cycles and biology of pathogenic trypanosomes. British Medical Bulletin 41, 105–114.CrossRefGoogle ScholarPubMed
Woods, A., Sherwin, T., Sasse, R., MacRae, T. H., Baines, A. J. and Gull, K. (1989). Definition of individual components within the cytoskeleton of Trypanosoma brucei by a library of monoclonal antibodies. Journal of Cell Science 93, 491–500.CrossRefGoogle ScholarPubMed
Zhou, Q., Gheiratmand, L., Chen, Y., Lim, T. K., Zhang, J., Li, S., Xia, N., Liu, B., Lin, Q. and He, C. Y. (2010). A comparative proteomic analysis reveals a new bi-lobe protein required for bi-lobe duplication and cell division in Trypanosoma brucei. PLoS One 5(3), e9660.CrossRefGoogle ScholarPubMed