trypanosoma variant surface glycoproteins

Summary

Summary: Glycoproteins attached to the surface coat of the trypanosome. Many of these glycoproteins show amino acid sequence diversity expressed as antigenic variations. This continuous development of antigenically distinct variants in the course of infection ensures that some trypanosomes always survive the development of immune response to propagate the infection.

Top Publications

  1. ncbi GPI anchor transamidase of Trypanosoma brucei: in vitro assay of the recombinant protein and VSG anchor exchange
    Xuedong Kang
    Physiologisch Chemisches Institut, University of Tubingen, Germany
    J Cell Sci 115:2529-39. 2002
  2. pmc Glycosylphosphatidylinositol-dependent protein trafficking in bloodstream stage Trypanosoma brucei
    Veronica P Triggs
    Department of Biomolecular Chemistry, University of Wisconsin Madison Medical School, Madison, Wisconsin 53706, USA
    Eukaryot Cell 2:76-83. 2003
  3. ncbi Telomere structure and function in trypanosomes: a proposal
    Oliver Dreesen
    The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
    Nat Rev Microbiol 5:70-5. 2007
  4. ncbi Hydrodynamic flow-mediated protein sorting on the cell surface of trypanosomes
    Markus Engstler
    Institut fur Mikrobiologie und Genetik, Technische Universitat Darmstadt, Schnittspahnstrasse 10, 64287, Darmstadt, Germany
    Cell 131:505-15. 2007
  5. pmc A histone methyltransferase modulates antigenic variation in African trypanosomes
    Luisa M Figueiredo
    Laboratory of Molecular Parasitology, Rockefeller University, New York, New York, USA
    PLoS Biol 6:e161. 2008
  6. ncbi A pol I transcriptional body associated with VSG mono-allelic expression in Trypanosoma brucei
    M Navarro
    Present address Instituto de Parasitología y Biomedicina López Neyra, CSIC, C Ventanilla 11, 18001 Granada, Spain
    Nature 414:759-63. 2001
  7. ncbi The structure, biosynthesis and functions of glycosylphosphatidylinositol anchors, and the contributions of trypanosome research
    M A Ferguson
    Division of Molecular Parasitology and Biological Chemistry, Department of Biochemistry, The Wellcome Trust Building, University of Dundee, Dundee DD1 5EH, UK
    J Cell Sci 112:2799-809. 1999
  8. ncbi Kinetics of endocytosis and recycling of the GPI-anchored variant surface glycoprotein in Trypanosoma brucei
    Markus Engstler
    Ludwigs Maximilians Universität, Department Biologie I, Bereich Genetik, Maria Ward Strasse 1a, D 80638 München, Germany
    J Cell Sci 117:1105-15. 2004
  9. pmc A role for RAD51 and homologous recombination in Trypanosoma brucei antigenic variation
    R McCulloch
    The Wellcome Centre for Molecular Parasitology, The Anderson College, University of Glasgow, Glasgow G11 6NU, U K
    Genes Dev 13:2875-88. 1999
  10. pmc A yeast-endonuclease-generated DNA break induces antigenic switching in Trypanosoma brucei
    Catharine E Boothroyd
    Laboratory of Lymphocyte Biology, The Rockefeller University, New York, New York 10065, USA
    Nature 459:278-81. 2009

Detail Information

Publications154 found, 100 shown here

  1. ncbi GPI anchor transamidase of Trypanosoma brucei: in vitro assay of the recombinant protein and VSG anchor exchange
    Xuedong Kang
    Physiologisch Chemisches Institut, University of Tubingen, Germany
    J Cell Sci 115:2529-39. 2002
    ..VSG-hydrazine-biotin was detected by streptavidin in western blots and intracellularly in Golgi-like compartments...
  2. pmc Glycosylphosphatidylinositol-dependent protein trafficking in bloodstream stage Trypanosoma brucei
    Veronica P Triggs
    Department of Biomolecular Chemistry, University of Wisconsin Madison Medical School, Madison, Wisconsin 53706, USA
    Eukaryot Cell 2:76-83. 2003
    ..A working model is proposed in which GPI valence regulates progression in the secretory pathway of bloodstream stage trypanosomes...
  3. ncbi Telomere structure and function in trypanosomes: a proposal
    Oliver Dreesen
    The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
    Nat Rev Microbiol 5:70-5. 2007
    ....
  4. ncbi Hydrodynamic flow-mediated protein sorting on the cell surface of trypanosomes
    Markus Engstler
    Institut fur Mikrobiologie und Genetik, Technische Universitat Darmstadt, Schnittspahnstrasse 10, 64287, Darmstadt, Germany
    Cell 131:505-15. 2007
    ....
  5. pmc A histone methyltransferase modulates antigenic variation in African trypanosomes
    Luisa M Figueiredo
    Laboratory of Molecular Parasitology, Rockefeller University, New York, New York, USA
    PLoS Biol 6:e161. 2008
    ..We conclude that DOT1B is required to maintain strict VSG silencing and to ensure rapid transcriptional VSG switching, demonstrating that epigenetics plays an important role in regulating antigenic variation in T. brucei...
  6. ncbi A pol I transcriptional body associated with VSG mono-allelic expression in Trypanosoma brucei
    M Navarro
    Present address Instituto de Parasitología y Biomedicina López Neyra, CSIC, C Ventanilla 11, 18001 Granada, Spain
    Nature 414:759-63. 2001
    ..We propose that the recruitment of a single expression site and the concomitant exclusion of inactive loci from a discrete transcriptional body define the mechanism responsible for VSG mono-allelic expression...
  7. ncbi The structure, biosynthesis and functions of glycosylphosphatidylinositol anchors, and the contributions of trypanosome research
    M A Ferguson
    Division of Molecular Parasitology and Biological Chemistry, Department of Biochemistry, The Wellcome Trust Building, University of Dundee, Dundee DD1 5EH, UK
    J Cell Sci 112:2799-809. 1999
    ..Apart from providing stable membrane anchorage, GPI anchors have been implicated in the sequestration of GPI-anchored proteins into specialised membrane microdomains, known as lipid rafts, and in signal transduction events...
  8. ncbi Kinetics of endocytosis and recycling of the GPI-anchored variant surface glycoprotein in Trypanosoma brucei
    Markus Engstler
    Ludwigs Maximilians Universität, Department Biologie I, Bereich Genetik, Maria Ward Strasse 1a, D 80638 München, Germany
    J Cell Sci 117:1105-15. 2004
    ..VSG recycling provides an interesting model for studies on the cellular trafficking and sorting of GPI-anchored proteins...
  9. pmc A role for RAD51 and homologous recombination in Trypanosoma brucei antigenic variation
    R McCulloch
    The Wellcome Centre for Molecular Parasitology, The Anderson College, University of Glasgow, Glasgow G11 6NU, U K
    Genes Dev 13:2875-88. 1999
    ..Switching events were still detectable, however, so it appears that trypanosome factors other than RAD51 can also provide for antigenic variation...
  10. pmc A yeast-endonuclease-generated DNA break induces antigenic switching in Trypanosoma brucei
    Catharine E Boothroyd
    Laboratory of Lymphocyte Biology, The Rockefeller University, New York, New York 10065, USA
    Nature 459:278-81. 2009
    ....
  11. ncbi A multiplex PCR that discriminates between Trypanosoma brucei brucei and zoonotic T. b. rhodesiense
    Kim Picozzi
    Centre for Infectious Diseases, College of Medicine and Veterinary Medicine, Royal Dick School of Veterinary Science, The University of Edinburgh, Edinburgh EH25 9RG, UK
    Exp Parasitol 118:41-6. 2008
    ..b. rhodesiense), inclusion of GPI-PLC as an internal control indicates whether sufficient genomic material is present for detection of a single copy T. brucei gene in the PCR reaction...
  12. ncbi Transcription of 'inactive' expression sites in African trypanosomes leads to expression of multiple transferrin receptor RNAs in bloodstream forms
    I Ansorge
    Zentrum fur Molekulare Biologie, Universitat Heidelberg, Germany
    Mol Biochem Parasitol 101:81-94. 1999
    ..This suggests a simplified model of VSG expression site control, whereby the only regulated event is the strong activation of a single expression site promoter in bloodstream forms...
  13. ncbi Nuclear architecture underlying gene expression in Trypanosoma brucei
    Miguel Navarro
    Instituto de Parasitologia y Biomedicina Lopez Neyra, Consejo Superior de Investigaciones Científicas Spanish National Research Council, Avda del Conocimiento s n, 18100 Granada, Spain
    Trends Microbiol 15:263-70. 2007
    ..Here, we discuss recent advances in understanding the role of chromosomal nuclear positioning in the regulation of gene expression in T. brucei...
  14. ncbi Two pathways of homologous recombination in Trypanosoma brucei
    Colin Conway
    The Wellcome Centre for Molecular Parasitology, The Anderson College, University of Glasgow, UK
    Mol Microbiol 45:1687-700. 2002
    ..We show that the RAD51-independent pathway is capable of recombining DNA substrates with very short lengths of sequence homology and in some cases aberrant recombination reactions can be detected using such microhomologies...
  15. ncbi Efficient targeting of conserved cryptic epitopes of infectious agents by single domain antibodies. African trypanosomes as paradigm
    Benoit Stijlemans
    Department of Cellular and Molecular Interactions, Vlaams Interuniversitair Instituut voor Biotechnologie, Vrije Universiteit Brussel, Pleinlaan 2, B 1050 Brussels, Belgium
    J Biol Chem 279:1256-61. 2004
    ..This was illustrated by the specific trypanolysis induced by an antibody::beta-lactamase fusion activating a prodrug...
  16. ncbi Antigenic variation and allelic exclusion
    Piet Borst
    The Netherlands Cancer Institute, Division of Molecular Biology and Center for Biomedical Genetics, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
    Cell 109:5-8. 2002
    ..The possibility that such a structure might explain monoallelic expression in other multigene systems is discussed here...
  17. ncbi Antigenic variation in trypanosomes: secrets surface slowly
    G A Cross
    Rockefeller University, New York, NY 10021 6399, USA
    Bioessays 18:283-91. 1996
    ..There is every reason to expect trypanosomes to provide further surprises and insights into the evolution of genetic regulatory mechanisms...
  18. ncbi Ku is important for telomere maintenance, but not for differential expression of telomeric VSG genes, in African trypanosomes
    Colin Conway
    Wellcome Centre for Molecular Parasitology, University of Glasgow, Anderson College, 56 Dumbarton Road, Glasgow, G11 6NU, Scotland, United Kingdom
    J Biol Chem 277:21269-77. 2002
    ..The absence of Ku and the consequent great shortening of telomeres had no detectable influence either on the rate of VSG switching or on the silencing of the telomeric promoters of the VSG subset that is expressed in the tsetse fly...
  19. pmc Analysis of the VSG gene silent archive in Trypanosoma brucei reveals that mosaic gene expression is prominent in antigenic variation and is favored by archive substructure
    Lucio Marcello
    Wellcome Centre for Molecular Parasitology, University of Glasgow, Glasgow Biomedical Research Centre, Glasgow G12 8TA, United Kingdom
    Genome Res 17:1344-52. 2007
    ..The small subfamily structure of the archive appears to be fundamental in providing the interacting donors for mosaic formation...
  20. ncbi Identification of a glycosylphosphatidylinositol anchor-modifying beta1-3 N-acetylglucosaminyl transferase in Trypanosoma brucei
    Luis Izquierdo
    Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    Mol Microbiol 71:478-91. 2009
    ..However, changes in the lectin binding of other glycoproteins suggest that TbGT8 influences the processing of the poly N-acetyllactosamine-containing asparagine-linked glycans of this life cycle stage...
  21. pmc Hemizygous subtelomeres of an African trypanosome chromosome may account for over 75% of chromosome length
    Sergio Callejas
    Department of Pathology, University of Cambridge, CB2 1QP, Cambridge, United Kingdom
    Genome Res 16:1109-18. 2006
    ..Further experimentation is required to determine if these results are applicable to all size-variable chromosomes...
  22. pmc Nuclear repositioning of the VSG promoter during developmental silencing in Trypanosoma brucei
    David Landeira
    Instituto de Parasitologia y Biomedicina Lopez Neyra, Consejo Superior de Investigaciones Cientificas, Spanish National Research Council, 18100 Granada, Spain
    J Cell Biol 176:133-9. 2007
    ..Subsequently, the VSG promoter region was subjected to chromatin condensation. We propose a model whereby the VSG expression site pol I promoter is selectively targeted by temporal nuclear repositioning during developmental silencing...
  23. pmc Expression and cellular localization of molecules of the gp82 family in Trypanosoma cruzi metacyclic trypomastigotes
    Vanessa D Atayde
    Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Rua Botucatu 862 6o andar, 04023 062 Sao Paulo, S P, Brazil
    Infect Immun 75:3264-70. 2007
    ..Host cell invasion of metacyclic forms was inhibited by J18 protein, as well as by MAb 3F6 and anti-J18 antibodies, but not by C03 protein or anti-C03 antibodies...
  24. ncbi Antigenic variation in trypanosomes: enhanced phenotypic variation in a eukaryotic parasite
    J D Barry
    Wellcome Centre for Molecular Parasitology, University of Glasgow, Scotland, UK
    Adv Parasitol 49:1-70. 2001
    ....
  25. pmc Telomere length regulation and transcriptional silencing in KU80-deficient Trypanosoma brucei
    Christian J Janzen
    Laboratory of Molecular Parasitology, The Rockefeller University, Box 185, 1230 York Avenue, New York, NY 10021 6399, USA
    Nucleic Acids Res 32:6575-84. 2004
    ..Finally, we demonstrated progressive telomere shortening in tbKU80-deficient mutants. The possible function of tbKU80 in telomere maintenance and regulation of telomerase is discussed...
  26. ncbi The transferrin receptor of Trypanosoma brucei
    D Steverding
    Abteilung Parasitologie, Hygiene Institut, Ruprecht Karls Universitat, Im Neuenheimer Feld 324, D 69120 Heidelberg, Germany
    Parasitol Int 48:191-8. 2000
    ..In this review, the structure, biochemical properties and function of the transferrin receptor of T. brucei are summarized and compared to the transferrin receptor of mammalian cells...
  27. pmc RNA polymerase I transcribes procyclin genes and variant surface glycoprotein gene expression sites in Trypanosoma brucei
    ARTHUR GUNZL
    Medizinisch Naturwissenschaftliches Forschungsinstitut der Universität Tübingen, 72074 Tubingen, Germany
    Eukaryot Cell 2:542-51. 2003
    ..Our studies unequivocally show that T. brucei harbors a multifunctional RNA pol I which, in addition to transcribing rDNA, transcribes procyclin genes and VSG gene expression sites...
  28. ncbi The VSG expression sites of Trypanosoma brucei: multipurpose tools for the adaptation of the parasite to mammalian hosts
    E Pays
    Laboratory of Molecular Parasitology, IBMM, Department of Molecular Biology, Free University of Brussels, 12, rue des Professeurs Jeener et Brachet, B 6041, Gosselies, Belgium
    Mol Biochem Parasitol 114:1-16. 2001
    ..The high transcription rate and high recombination level that prevail in VSG ESs may have favored the generation and/or recruitment in these sites of genes whose hyper-evolution allows adaptation to a larger variety of hosts...
  29. ncbi The properties and function of the glycosylphosphatidylinositol-phospholipase C in Trypanosoma brucei
    M Carrington
    Department of Biochemistry, Cambridge, UK
    Mol Biochem Parasitol 91:153-64. 1998
    ..The phenotype indicates that the gene is non-essential, but its absence alters the course of infection in mice...
  30. pmc Chaperone requirements for biosynthesis of the trypanosome variant surface glycoprotein
    Mark C Field
    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    PLoS ONE 5:e8468. 2010
    ..As the variant surface glycoprotein (VSG) represents approximately 90% of trypanosome plasma membrane protein, it is possible that VSG has evolved to fold efficiently to minimize ER folding burden...
  31. pmc A function for a specific zinc metalloprotease of African trypanosomes
    Paul M Grandgenett
    Interdepartmental Genetics Program, University of Iowa, Iowa City, Iowa, USA
    PLoS Pathog 3:1432-45. 2007
    ..Inhibitors of cysteine proteases did not affect this result. These findings demonstrate that removal of 60% of the VSG during differentiation from bloodstream to procyclic form is due to the synergistic activities of GPI-PLC and TbMSP-B...
  32. pmc A novel ISWI is involved in VSG expression site downregulation in African trypanosomes
    Katie Hughes
    Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK
    EMBO J 26:2400-10. 2007
    ..VSG ES activation in African trypanosomes therefore appears to be a multistep process, whereby an increase in transcription from a silent ES promoter is necessary but not sufficient for full ES activation...
  33. ncbi Bloodstream form-specific up-regulation of silent vsg expression sites and procyclin in Trypanosoma brucei after inhibition of DNA synthesis or DNA damage
    Karen Sheader
    The Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford OX1 3SY, United Kingdom
    J Biol Chem 279:13363-74. 2004
    ..brucei. We postulate that the redistribution of a limiting bloodstream form-specific factor involved in both silencing and DNA repair results in the derepression of normally silenced pol I transcription units after DNA damage...
  34. ncbi Control of VSG gene expression sites
    P Borst
    The Netherlands Cancer Institute, Division of Molecular Biology and Centre of Biomedical Genetics, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
    Mol Biochem Parasitol 114:17-27. 2001
    ..This review summarizes recent work on the mechanism of site switching and on the way inactive expression sites are kept silent...
  35. ncbi Deletion of the glucosidase II gene in Trypanosoma brucei reveals novel N-glycosylation mechanisms in the biosynthesis of variant surface glycoprotein
    Deuan C Jones
    Division of Biological Chemistry and Molecular Microbiology, School of Life Sciences, The Wellcome Trust Biocentre, University of Dundee, Dundee DD1 5EH, United Kingdom
    J Biol Chem 280:35929-42. 2005
    ....
  36. ncbi The central roles of telomeres and subtelomeres in antigenic variation in African trypanosomes
    David Horn
    London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Chromosome Res 13:525-33. 2005
    ..Current research addresses the role of telomeres in the conversion and silencing mechanisms and in the diversification of the VSG archive...
  37. ncbi Antigenic variation in Trypanosoma brucei: facts, challenges and mysteries
    Etienne Pays
    Laboratory of Molecular Parasitology, IBMM, Free University of Brussels, 12, rue des Professeurs Jeener et Brachet, B6041 Gosselies, Belgium
    Curr Opin Microbiol 7:369-74. 2004
    ..So far, the identification of mechanisms and factors involved still resists technological developments and genome sequencing...
  38. pmc VSG switching in Trypanosoma brucei: antigenic variation analysed using RNAi in the absence of immune selection
    Niall Aitcheson
    Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford OX1 3SY, UK
    Mol Microbiol 57:1608-22. 2005
    ..Most of the preferentially activated VSGs could be activated by multiple mechanisms. This VSG RNAi-based procedure provides a rapid and powerful means for analysing VSG switching in African trypanosomes entirely in vitro...
  39. ncbi Regulation of surface coat exchange by differentiating African trypanosomes
    Amy E Gruszynski
    Department of Biomolecular Chemistry, University of Wisonsin Madison, 1300 University Avenue, Madison, WI 53706, USA
    Mol Biochem Parasitol 147:211-23. 2006
    ..The relegation of short stumpy surface GPI-PLC to a secondary role in differentiation suggests that it may play a more important role as a virulence factor within the mammalian host...
  40. ncbi Trypanosoma cruzi surface molecule gp90 downregulates invasion of gastric mucosal epithelium in orally infected mice
    Mauro Cortez
    Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, R Botucatu, 862 6 andar, 04023 062 Sao Paulo, SP, Brazil
    Microbes Infect 8:36-44. 2006
    ..Our data indicate that T. cruzi infection in vitro does not always correlate with in vivo infection because host factors may act on parasites, modulating their infectivity, as is the case of pepsin digestion of isolate 573 gp90...
  41. pmc Streamlined architecture and glycosylphosphatidylinositol-dependent trafficking in the early secretory pathway of African trypanosomes
    Elitza S Sevova
    Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA
    Mol Biol Cell 20:4739-50. 2009
    ..This unusual architecture probably maximizes efficiency of VSG transport and fidelity in organellar segregation during cytokinesis...
  42. ncbi Mild acid stress as a differentiation trigger in Trypanosoma brucei
    S Rolin
    Department of Molecular Biology, Free University of Brussels, Rhode St Genese, Belgium
    Mol Biochem Parasitol 93:251-62. 1998
    ..However, an effective response was restored upon reintegration of the GPI-PLC gene in the genome (PLC+)...
  43. pmc Endocytosis of a glycosylphosphatidylinositol-anchored protein via clathrin-coated vesicles, sorting by default in endosomes, and exocytosis via RAB11-positive carriers
    Christoph G Grünfelder
    Max Planck Institut fur Biologie, Abteilung Membranbiochemie, D 72076 Tubingen, Germany
    Mol Biol Cell 14:2029-40. 2003
    ....
  44. pmc De novo sphingolipid synthesis is essential for viability, but not for transport of glycosylphosphatidylinositol-anchored proteins, in African trypanosomes
    Shaheen S Sutterwala
    Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA
    Eukaryot Cell 6:454-64. 2007
    ..However, in contrast to the closely related kinetoplastid Leishmania major, de novo sphingolipid synthesis is essential for the viability of bloodstream-stage African trypanosomes...
  45. ncbi CR3 (CD11b/CD18) is the major macrophage receptor for IgM antibody-mediated phagocytosis of African trypanosomes: diverse effect on subsequent synthesis of tumor necrosis factor alpha and nitric oxide
    Wanling Pan
    Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK S7N 5B4, Canada
    Microbes Infect 8:1209-18. 2006
    ..congolense enhances synthesis of disease-producing TNF-alpha and inhibits synthesis of parasite-controlling NO. We suggest that signaling of inhibition of NO synthesis is mediated via CR3...
  46. ncbi The serum resistance-associated gene as a diagnostic tool for the detection of Trypanosoma brucei rhodesiense
    Magdalena Radwanska
    Department of Parasitology, Institute of Tropical Medicine, Antwerp, Belgium
    Am J Trop Med Hyg 67:684-90. 2002
    ..b. rhodesiense in 17 of 17 SRA gene-positive strains in which it was tested. These data strongly suggest that expression of the SRA gene is generally involved in resistance to lysis by NHS in T. b. rhodesiense strains...
  47. pmc Deletion of a trypanosome telomere leads to loss of silencing and progressive loss of terminal DNA in the absence of cell cycle arrest
    Lucy Glover
    London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK
    Nucleic Acids Res 35:872-80. 2007
    ..The results provide direct evidence for telomere-dependent repression but suggest a telomere-independent mode of VSG-silencing. They also indicate the absence of a telomere-loss checkpoint in T. brucei...
  48. ncbi The molecular control of antigenic variation in Trypanosoma brucei
    David Horn
    Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Curr Mol Med 4:563-76. 2004
    ....
  49. pmc Rab5 and Rab11 mediate transferrin and anti-variant surface glycoprotein antibody recycling in Trypanosoma brucei
    Arun Pal
    Wellcome Trust Laboratories for Molecular Parasitology, Department of Biological Sciences and Centre for Molecular Microbiology and Infection, Imperial College London, London, SW7 2AY, UK
    Biochem J 374:443-51. 2003
    ..The presence of an efficient mechanism for the removal of IgG bound to the external surface of T. brucei and its subsequent proteolysis within the recycling system suggests a role for this pathway in immune evasion...
  50. ncbi Mismatch repair regulates homologous recombination, but has little influence on antigenic variation, in Trypanosoma brucei
    Joanna S Bell
    Wellcome Centre for Molecular Parasitology, University of Glasgow, Anderson College, 56 Dumbarton Road, Glasgow G11 6NU, Scotland, United Kingdom
    J Biol Chem 278:45182-8. 2003
    ....
  51. pmc Repression of polymerase I-mediated gene expression at Trypanosoma brucei telomeres
    Lucy Glover
    London School of Hygiene and Tropical Medicine, London, UK
    EMBO Rep 7:93-9. 2006
    ..Our results show constitutive telomeric repression in T. brucei and indicate that an enhanced, developmental stage-specific repression mechanism controls antigenic variation...
  52. ncbi Probabilistic order in antigenic variation of Trypanosoma brucei
    Liam J Morrison
    Wellcome Centre for Molecular Parasitology, University of Glasgow, 56 Dumbarton Rd, Glasgow, G11 6NU, Scotland, UK
    Int J Parasitol 35:961-72. 2005
    ....
  53. ncbi Regulation of antigen gene expression in Trypanosoma brucei
    Etienne Pays
    Laboratory of Molecular Parasitology, Institut de Biologie Moléculaire et Médicale, Universite Libre de Bruxelles, 12 rue des Professeurs Jeener et Brachet, B6041 Gosselies, Belgium
    Trends Parasitol 21:517-20. 2005
    ..The high recombination frequency prevailing in the telomere that harbours the active VSG expression site has been exploited by the parasite to both drive antigenic variation and generate VSG-based adaptive proteins...
  54. ncbi The Trypanosoma brucei reference strain TREU927/4 contains T. brucei rhodesiense-specific SRA sequences, but displays a distinct phenotype of relative resistance to human serum
    Luc Vanhamme
    Laboratory of Molecular Parasitology, Department of Molecular Biology, IBMM, Free University of Brussels, 12, rue des Professeurs Jeener et Brachet, B 6041 Gosselies, Belgium
    Mol Biochem Parasitol 135:39-47. 2004
    ....
  55. ncbi Regulation of innate and acquired immunity in African trypanosomiasis
    J M Mansfield
    Department of Bacteriology, University of Wisconsin Madison, Madison, WI 53706, USA
    Parasite Immunol 27:361-71. 2005
    ..The biological relevance of these immunoregulatory events is discussed in the context of host and parasite survival...
  56. ncbi Accumulation of a GPI-anchored protein at the cell surface requires sorting at multiple intracellular levels
    Christoph G Grünfelder
    Max Planck Institut fur Biologie, Abteilung Membranbiochemie, Corrensstrasse 38, D 72076 Tubingen, Germany
    Traffic 3:547-59. 2002
    ....
  57. ncbi Loss of the mono-allelic control of the VSG expression sites during the development of Trypanosoma brucei in the bloodstream
    Amelia Amiguet-Vercher
    Laboratory of Molecular Parasitology, IBMM, Free University of Brussels, 12, rue des Professeurs Jeener et Brachet, B 6041 Gosselies, Belgium
    Mol Microbiol 51:1577-88. 2004
    ..This inactivation is accompanied by a strong overall reduction of nuclear DNA transcription. Although cAMP is involved in the LS to SS transformation, no direct effect of cAMP was observed on the VSG ES control...
  58. ncbi Surface coat remodeling during differentiation of Trypanosoma brucei
    Amy E Gruszynski
    Department of Biomolecular Chemistry, University of Wisconsin Medical School, Madison 53706, USA
    J Biol Chem 278:24665-72. 2003
    ..2003) J. Biol. Chem. 278, 24658-24664). Overall, our results demonstrate that surface coat remodeling during differentiation has multiple mechanisms and that GPI-PLC plays a more significant role in VSG release than previously thought...
  59. ncbi What the genome sequence is revealing about trypanosome antigenic variation
    J D Barry
    University of Glasgow, Glasgow G12 8QQ, Scotland, UK
    Biochem Soc Trans 33:986-9. 2005
    ..These findings from the genome project have major implications for evolution of the VSG archive and for transmission of the parasite in the field...
  60. ncbi Delineation of the regulated Variant Surface Glycoprotein gene expression site domain of Trypanosoma brucei
    Karen Sheader
    The Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford OX1 3SY, UK
    Mol Biochem Parasitol 128:147-56. 2003
    ..Therefore, the 50 bp repeat arrays appear to be the boundary of the regulated expression site domain...
  61. ncbi VSG structure: similar N-terminal domains can form functional VSGs with different types of C-terminal domain
    Oliver Clyde Hutchinson
    Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK
    Mol Biochem Parasitol 130:127-31. 2003
  62. ncbi Antigenic variation and the African trypanosome genome
    John E Donelson
    Department of Biochemistry, University of Iowa, Iowa City, IA 52242, USA
    Acta Trop 85:391-404. 2003
    ..Progress in sequencing the African trypanosome genome has led to additional insights on the organization of genes within both groups of ESs that may ultimately suggest better ways to control or eliminate this deadly pathogen...
  63. pmc Application of electrospray mass spectrometry to the structural determination of glycosylphosphatidylinositol membrane anchors
    Isabelle R E Nett
    Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Glycobiology 20:576-85. 2010
    ....
  64. ncbi The genes and transcripts of an antigen gene expression site from T. brucei
    E Pays
    Department of Molecular Biology, Free University of Brussels, Belgium
    Cell 57:835-45. 1989
    ..Ultraviolet irradiation, which seems to block RNA processing, allows the tentative mapping of a transcription promoter about 45 kb upstream of the antigen gene...
  65. ncbi Macromolecular trafficking and immune evasion in african trypanosomes
    Mark C Field
    Department of Pathology, University of Cambridge, Cambridge CB2 1QT, United Kingdom
    Int Rev Cell Mol Biol 278:1-67. 2009
    ..Here, we discuss current understanding of intracellular trafficking pathways of trypanosomes, and relate these processes to immune evasion strategies by the parasite and avoidance of immune responses from the host...
  66. ncbi Cloning of a novel surface antigen from the insect stages of Trypanosoma brucei by expression in COS cells
    D G Jackson
    Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, England
    J Biol Chem 268:1894-900. 1993
    ..Southern blot hybridization analysis of DNA from procyclic stage trypanosomes indicated that the gene for PSSA-2 may be present in more than one copy in procyclic trypanosomes...
  67. ncbi Diversity and dynamics of the minichromosomal karyotype in Trypanosoma brucei
    S Alsford
    School of Biological Sciences, University of Manchester, 2.205 Stopford Building, Oxford Road, Manchester M13 9PT, UK
    Mol Biochem Parasitol 113:79-88. 2001
    ..This steady telomeric growth, counteracted by stochastic large losses of telomeric sequences is the most likely cause of minichromosome karyotype heterogeneity within a population...
  68. pmc Trypanosoma brucei BRCA2 acts in antigenic variation and has undergone a recent expansion in BRC repeat number that is important during homologous recombination
    Claire L Hartley
    The Wellcome Centre for Molecular Parasitology and Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow Biomedical Research Centre, 120 University Place, Glasgow G12 8TA, UK
    Mol Microbiol 68:1237-51. 2008
    ..brucei homologous recombination and RAD51 localization. Remarkably, however, this appears not to be a major determinant of the activation of at least some VSG genes...
  69. ncbi CD1d-restricted immunoglobulin G formation to GPI-anchored antigens mediated by NKT cells
    L Schofield
    Walter and Eliza Hall Institute of Medical Research, Post Office, Royal Melbourne Hospital, Victoria 3050, Australia
    Science 283:225-9. 1999
    ..The CD1-NKT cell pathway regulated immunogobulin G responses to the GPI-anchored surface antigens of Plasmodium and Trypanosoma and may be a general mechanism for rapid, MHC-unrestricted antibody responses to diverse pathogens...
  70. ncbi Trypanosoma congolense: B-lymphocyte responses differ between trypanotolerant and trypanosusceptible cattle
    K A Taylor
    International Livestock Research Institute, Nairobi, Kenya
    Exp Parasitol 83:106-16. 1996
    ..congolense...
  71. pmc T-cell responses to the trypanosome variant surface glycoprotein are not limited to hypervariable subregions
    Taylor R Dagenais
    Department of Bacteriology, Microbial Sciences Building, 1550 Linden Drive, University of Wisconsin Madison, Madison, WI 53706, USA
    Infect Immun 77:141-51. 2009
    ....
  72. ncbi The rate of antigenic variation in fly-transmitted and syringe-passaged infections of Trypanosoma brucei
    C M Turner
    Division of Infection and Immunity, I B L S, University of Glasgow, UK
    FEMS Microbiol Lett 153:227-31. 1997
    ..They also show that the reduction in switching rate associated with syringe passaging is reversible and is thus unlikely to be caused by mutation...
  73. pmc Expression of bloodstream variant surface glycoproteins in procyclic stage Trypanosoma brucei: role of GPI anchors in secretion
    J D Bangs
    Department of Medical Microbiology and Immunology, University of Wisconsin Madison Medical School, 53706, USA
    EMBO J 16:4285-94. 1997
    ..This unexpected result suggests that GPI processing may be influenced by adjacent peptide sequence or conformation...
  74. ncbi The molecular karyotype of the megabase chromosomes of Trypanosoma brucei stock 427
    S E Melville
    Department of Pathology, University of Cambridge, UK
    Mol Biochem Parasitol 111:261-73. 2000
    ..We propose that the chromosomes of stock 427 be numbered to correspond to their homologues in the genome project reference stock TREU 927/4...
  75. pmc VSGdb: a database for trypanosome variant surface glycoproteins, a large and diverse family of coiled coil proteins
    Lucio Marcello
    Wellcome Centre for Molecular Parasitology, University of Glasgow, Glasgow Biomedical Research Centre, Glasgow, UK
    BMC Bioinformatics 8:143. 2007
    ..To enable ready availability of VSG sequences for addressing these general questions, and trypanosome-specific questions, we have created VSGdb, a database of all known sequences...
  76. pmc RNA polymerase I transcription stimulates homologous recombination in Trypanosoma brucei
    Sam Alsford
    London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Mol Biochem Parasitol 153:77-9. 2007
  77. ncbi The glycoforms of a Trypanosoma brucei variant surface glycoprotein and molecular modeling of a glycosylated surface coat
    Angela Mehlert
    Division of Biological Chemistry and Molecular Microbiology, The Wellcome Trust Biocentre, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Glycobiology 12:607-12. 2002
    ..Using the most abundant oligosaccharides at each site, we construct a molecular model of the glycoprotein to assess the role of N-linked oligosaccharides in the architecture of the surface coat...
  78. ncbi The architecture of variant surface glycoprotein gene expression sites in Trypanosoma brucei
    Matthew Berriman
    The Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK
    Mol Biochem Parasitol 122:131-40. 2002
    ..Unexpected conservation of sequences, including pseudogenes, indicates that the multiple ESs could have arisen through a relatively recent amplification of a single ES...
  79. ncbi Switching trypanosome coats: what's in the wardrobe?
    Jesse E Taylor
    Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford OX1 3SY, UK
    Trends Genet 22:614-20. 2006
    ..This preponderance of pseudogenes in the VSG gene repertoire will necessitate a rethink of how antigenic variation in African trypanosomes operates...
  80. ncbi Immunology and immunopathology of African trypanosomiasis
    Philippe Vincendeau
    Laboratoire de Parasitologie, Universite de Bordeaux II, Bordeaux, France
    An Acad Bras Cienc 78:645-65. 2006
    ..L-ornithine produced by host arginase is essential to parasite growth. All these data reflect the deep insight into the immune system realised by trypanosomes and might suggest interference therapeutic approaches...
  81. ncbi Mutational analysis of the variant surface glycoprotein GPI-anchor signal sequence in Trypanosoma brucei
    Ulrike Böhme
    Laboratory of Molecular Parasitology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    J Cell Sci 115:805-16. 2002
    ..However, because the VSG is a major virulence factor, it is possible that small changes in the efficiency of GPI anchoring, undetectable in our experiments, might have influenced the evolution of VSG GPI signal sequences...
  82. pmc Trypanosoma brucei ARF1 plays a central role in endocytosis and golgi-lysosome trafficking
    Helen P Price
    Immunology and Infection Unit, Department of Biology, University of York, Heslington, York YO10 5YW, United Kingdom
    Mol Biol Cell 18:864-73. 2007
    ..We conclude that the essential Golgi-localizing T. brucei ARF1 has a primary role in the maintenance of both post-Golgi transport and endocytosis and that it is significantly divergent from other characterized ARFs...
  83. ncbi Fatty acid synthesis in African trypanosomes: a solution to the myristate mystery
    K S Paul
    Dept Biological Chemistry, Johns Hopkins Medical School, 725 N. Wolfe Street, Baltimore, MD 21205, USA
    Trends Parasitol 17:381-7. 2001
    ..The parasite not only efficiently salvages and processes myristate from the bloodstream, but it also makes myristate de novo using a recently discovered specialized fatty acid synthesis system...
  84. ncbi A family of stage-specific alanine-rich proteins on the surface of epimastigote forms of Trypanosoma brucei
    Simon Urwyler
    Institut fur Zellbiologie, Universitat Bern, Bern, Switzerland
    Mol Microbiol 63:218-28. 2007
    ..In contrast to an earlier report, we could not detect BARPs in bloodstream forms. We propose that BARPs form a stage-specific coat for epimastigote forms and suggest renaming them brucei alanine-rich proteins...
  85. ncbi Regulation of protein trafficking by glycosylphosphatidylinositol valence in African trypanosomes
    Kevin J Schwartz
    Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, Madison, Wisconsin 53711, USA
    J Eukaryot Microbiol 54:22-4. 2007
    ..Here we summarize recent data confirming this correlation using a tool kit of recombinant GPI anchored reporters, including a reporter designed to be conditionally modulated between a GPI valence of one and two...
  86. ncbi Implications of conserved structural motifs in disparate trypanosome surface proteins
    M Carrington
    University of Cambridge, Department of Biochemistry, UK
    Mol Biochem Parasitol 81:119-26. 1996
    ..These findings suggest that this master structure has evolved to facilitate a range of functions and has implications for understanding the architecture of the trypanosome cell surface and the origins of antigenic variation...
  87. ncbi The induction of a type 1 immune response following a Trypanosoma brucei infection is MyD88 dependent
    Michael B Drennan
    Immunology of Infectious Disease Medical Research Council University of Cape Town Unit, Institute of Infectious Disease and Molecular Medicine, Health Science Faculty, University of Cape Town, Cape Town, South Africa
    J Immunol 175:2501-9. 2005
    ..brucei infections. These results implicate the mammalian TLR family and MyD88 signaling in the innate immune recognition of T. brucei...
  88. pmc Isolation and analysis of the genetic diversity of repertoires of VSG expression site containing telomeres from Trypanosoma brucei gambiense, T. b. brucei and T. equiperdum
    Rosanna Young
    Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford, OX1 3SY, UK
    BMC Genomics 9:385. 2008
    ..We have previously developed a method to selectively isolate sets of trypanosome BES containing telomeres using Transformation associated recombination (TAR) cloning in yeast...
  89. pmc Telomere length in Trypanosoma brucei
    Oliver Dreesen
    Laboratory of Molecular Parasitology, The Rockefeller University, 1230 York Avenue, New York, NY 10021 6399, USA
    Exp Parasitol 118:103-10. 2008
    ..brucei have shorter telomeres than extensively propagated Lister 427 clones, suggesting a link between laboratory adaptation, telomere growth, and VSG switching rates...
  90. ncbi GPI valence and the fate of secretory membrane proteins in African trypanosomes
    Kevin J Schwartz
    Department of Medical Microbiology and Immunology, University of Wisconsin Madison Medical School, Madison, WI 53706, USA
    J Cell Sci 118:5499-511. 2005
    ..Surface receptor was non-functional for ligand binding suggesting that it may be bivalent homodimers of the GPI-anchored ESAG6 receptor subunit...
  91. ncbi A glycosylphosphatidylinositol-based treatment alleviates trypanosomiasis-associated immunopathology
    Benoit Stijlemans
    Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussels, Pleinlaan 2, Brussels, Belgium
    J Immunol 179:4003-14. 2007
    ....
  92. pmc Consequences of telomere shortening at an active VSG expression site in telomerase-deficient Trypanosoma brucei
    Oliver Dreesen
    Laboratory of Molecular Parasitology, The Rockefeller University, 1230 York Avenue, New York, NY 10021 6307, USA
    Eukaryot Cell 5:2114-9. 2006
    ..We propose a model in which subtelomeric-break-induced replication-mediated repair at a short ES telomere leads to duplicative gene conversion and expression of a new VSG...
  93. pmc Expression site silencing and life-cycle progression appear normal in Argonaute1-deficient Trypanosoma brucei
    Christian J Janzen
    Laboratory of Molecular Parasitology, The Rockefeller University, Box 185, 1230 York Avenue, New York, NY 10021 6399, USA
    Mol Biochem Parasitol 149:102-7. 2006
  94. pmc Developmental variation in Rab11-dependent trafficking in Trypanosoma brucei
    Belinda S Hall
    Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom
    Eukaryot Cell 4:971-80. 2005
    ..These data demonstrate that TbRAB11 controls recycling and is essential in both life stages of T. brucei but that its primary role is subject to developmental variation...
  95. pmc Targeting the variable surface of African trypanosomes with variant surface glycoprotein-specific, serum-stable RNA aptamers
    Mihaela Lorger
    Department of Microbiology and Genetics, Darmstadt University of Technology, 64287 Darmstadt, Germany
    Eukaryot Cell 2:84-94. 2003
    ..Aptamers tethered to an antigenic side group are capable of directing antibodies to the surface of the parasite in vitro. In this manner, the RNAs might provide a new strategy for a therapeutic intervention to fight sleeping sickness...
  96. ncbi Targeted disruption of expression site-associated gene-1 in bloodstream-form Trypanosoma brucei
    V B Carruthers
    Laboratory of Molecular Parasitology, Rockefeller University, New York, NY 10021 6399, USA
    Mol Biochem Parasitol 81:65-79. 1996
    ..We have therefore been unable to determine whether esag1 is an essential gene, or what function it fulfils, or whether any competent Esag1 protein is expressed in the mutant trypanosomes...
  97. ncbi Expression and function of surface proteins in Trypanosoma brucei
    E Pays
    Department of Molecular Biology, University of Brussels 67, Rhode St Genese, Belgium
    Mol Biochem Parasitol 91:3-36. 1998
  98. ncbi In-vitro competition analysis of procyclin gene and variant surface glycoprotein gene expression site transcription in Trypanosoma brucei
    G Laufer
    , Abteilung Zellbiologie, Auf der Morgenstelle 28, , Germany
    Mol Biochem Parasitol 113:55-65. 2001
    ..Despite this structural difference, our analysis provide evidence that GPEET and VSG ES promoters interact with a common factor that is also important for RRNA promoter transcription...
  99. ncbi Leaky transcription of variant surface glycoprotein gene expression sites in bloodstream african trypanosomes
    C M Alarcon
    Department of Biochemistry, University of Iowa, Iowa City, Iowa 52242, USA
    J Biol Chem 274:16884-93. 1999
    ..Certain VSGs are preferentially expressed in metacyclic versus bloodstream stages as a result of differences in ESAG expression and the proximity of the promoters to the vsg and telomere...
  100. ncbi ESAG11, a new VSG expression site-associated gene from Trypanosoma brucei
    M B Redpath
    Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK
    Mol Biochem Parasitol 111:223-8. 2000
  101. ncbi Cyclic AMP signaling in trypanosomatids
    C Naula
    University of Bern, Institute of General Microbiology, Switzerland
    Parasitol Today 16:35-8. 2000
    ..Here, Christina Naula and Thomas Seebeck summarize what is known about cAMP signal transduction in trypanosomatids...

Research Grants11

  1. GPI PHOSPHOLIPASE C OF T BRUCEI
    Kojo Mensa Wilmot; Fiscal Year: 2001
    ..In lieu of this long term aim, our specific aims are to (i) unravel the mechanisms which regulate GPI-PLC activity in vivo, and (ii) study enzymatic reaction mechanism of GPI-PLC. ..
  2. Novel phospholipases C in trypanosomatids
    Silvia Moreno; Fiscal Year: 2009
    ..abstract_text> ..
  3. AMASTIN/TUZIN GENE CLUSTER OF TRYPANOSOMA CRUZI
    JOHN DONELSON; Fiscal Year: 2001
    ..Finally, we will assess whether amastin and/or tuzin can serve a target antigens for an improved diagnostic test for T. cruzi infection. ..
  4. Zinc metalloprotease families in Trypansoma brucei
    JOHN DONELSON; Fiscal Year: 2009
    ....
  5. GP46 GENES AND PROTEIN EXPRESSION IN LEISHMANIA CHAGASI
    JOHN DONELSON; Fiscal Year: 2002
    ....
  6. A CHEMICALLY SYNTHETIC ANTI-TOXIC VACCINE AGAINST MALARI
    Louis Schofield; Fiscal Year: 2002
    ..Clinical immunity to malaria is acquired considerably earlier than anti-parasite immunity, and it is possible that this is mediated by anti-toxin mechanisms. ..
  7. Modulation of innate immunity by microbial factors
    DONNA PAULNOCK; Fiscal Year: 2006
    ..The ultimate goal is to uncover novel regulatory mechanisms associated with macrophage activation that can be exploited to provide greater resistance to disease. ..
  8. A High Throughput Assay to Identify Onhibitors of Trypanosome RNA Editing Ligase
    Nancy Ernst; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  9. STRUCTURE AND EXPRESSION OF PNEUMOCYSTIS ANTIGEN GENES
    James Stringer; Fiscal Year: 2009
    ..abstract_text> ..
  10. IMMUNOBIOLOGY OF MALARIA GLYCOSYLPHOSPHATIDYLINOSITOL
    Louis Schofield; Fiscal Year: 2001
    ..These areas are central to understanding the host/parasite interaction and the development of effective vaccines to several protozoal pathogens. ..
  11. MACROPHAGE ACTIVATION IN AFRICAN TRYPANOSOMIASIS
    DONNA PAULNOCK; Fiscal Year: 2006
    ..The ultimate goal is to uncover novel regulatory mechanisms associated with macrophage activation that can be exploited to provide greater resistance to disease. ..