Abstract
Antigenic variation in the African trypanosome is a consequence of changes in the composition of the surface coat which covers the entire surface of the trypanosome, when it is in the blood stream of its mammalian host (reviewed by Vickerman and Barry 1982). The surface coat is made up of a matrix of about 107 identical glycoprotein molecules which are known as the variant surface glycoproteins (VSGs), because each antigenically distinct variant can be characterised by the immunochemical profile of the VSG which is expressed at its surface. Much is known about the biochemistry of the VSGs, which are notable for the remarkable diversity within their amino acid sequences (reviewed in Turner 1982 a; Cross 1984). However, it is clear that all VSGs must have certain features in common. Thus, they must all be capable of forming a compact surface coat, about 12- to 15-mm thick (Vickerman 1969), be impermeable to soluble mediators of the immune system, such as antibody and complement, and be anchored firmly to the plasma membrane. Furthermore, all the VSGs are presumably produced through a common intracellular pathway, utilising the same biosynthetic machinery. Thus it is to be expected that this combination of structural demands and synthetic restraints will be reflected in conserved structural elements, and interference with the synthesis of such elements should therefore be a potent form of chemotherapy. It is the purpose of this review to discuss what is known about the biosynthesis of VSGs, and also to review our knowledge of one of the most intriguing features of VSG biochemistry, namely the unusual mode of attachment to, and ready release from, the plasma membrane.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Auffret CA, Turner MJ (1981) Variant specific antigens of Trypanosoma brucei exist in solution as glycoprotein dimers. Biochem J 193: 647–650
Baltz T, Baltz D, Pautrizel R (1976) Affinity of concanavalin A for Trypanosoma equiperdum: purification of the antigenic type specific glycoprotein fraction. Ann Immunol 127: 761–774
Baltz T, Giroud Ch, Baltz D, Duvillier G, Degand P, Demaille J, Pautrizel R (1982) The variable surface glycoproteins of Trypanosoma equiperdum are phosphorylated. EMBO J 1: 1393–1398
Baltz T, Duvillier G, Giroud Ch, Richet C, Baltz D, Degand P (1983) The variant surface glycoproteins of Trypanosoma equiperdum. Identification of a phosphorylated glycopeptide as the cross-reacting antigenic determinant. FEBS Lett 158: 174–178
Barbet AF, McGuire TC, Musoke AJ, Hirumi H (1979) Cross-reacting determinants in trypanosome surface antigens. In: Losos G, Charinard A (eds) Pathogenicity of trypanosmes. International Development Research Centre, Ottawa, pp 38–43
Barry JD, Vickerman K (1979) Trypanosoma brucei loss of variable antigens during transformation from bloodstream to procyclic forms in vitro. Exp Parasitol 49: 281–300
Black SJ, Hewett RS, Sendashonga CN (1982) Trypanosoma brucei variable surface coat is released by degenerating parasites but not by actively dividing parasites. Parasite. Immunol 4: 233–244
Boothroyd JC, Cross GAM (1982) Transcripts coding for different variant surface glycoproteins of Trypanosoma brucei have a short, identical exon at their 5′ end. Gene 20: 281–289
Boothroyd JC, Cross GAM, Hoeijmakers JHJ, Borst P (1980) A variant surface glycoprotein of Trypanosoma brucei synthesised with a C-terminal hydrophobic “tail” absent from purified glycoprotein. Nature 288: 624–626
Boothroyd JC, Paynter CA, Cross GAM, Bernards A, Borst P (1981) Variant surface glycoproteins of Trypanosoma brucei are synthesised with cleavable hydrophobic sequences at the carboxy and amino termini. Nucleic Acids Res 9: 4743–4745
Boothroyd JC, Paynter CA, Coleman SC, Cross GAM (1982) Complete nucleotide sequence of complementary DNA coding for a variant surface glycoprotein from Trypanosoma brucei. J Mol Biol 157: 547–556
Bordier C (1981) Phase separation of integral membrane proteins in Triton X114 solution. J Biol Chem 256: 1604–1607
Bowles DJ, Voorheis HP (1982) Release of coat from the plasma membrane of intact blood stream forms of Trypanosoma brucei requires Ca2+. FEBS Lett 139: 17–21
Brett CT, Voorheis HP (1980) Glycoprotein biosynthesis in Trypanosoma brucei. The glycosylation of glycoproteins located in and attached to the plasma membrane. Eur J Biochem 109: 139–150
Bridgen PJ, Cross GAM, Bridgen J (1976) N-terminal amino acid sequences of variant specific surface antigens from Trypanosoma brucei. Nature 263: 613–614
Brock CJ, Tanner MJA (1982) Structure and synthesis of integral membrane proteins. In: Chapman D (ed) Biological membranes, vol 4. Academic, London, pp 75–130
Campbell GH, Esser KM, Wellde BT, Diggs CL (1979) Isolation and characterisation of a new serodeme of Trypanosoma rhodesiense. Am J Trop Med Hyg 28: 974–983
Cardoso de Almeida ML (1983) The mode of attachment of VSGs to the plasma membrane of T. brucei. Ph D Thesis, University of Cambridge, Cambridge
Cardoso de Almeida ML, Turner MJ (1983) The membrane form of variant surface glycoproteins of Trypanosoma brucei. Nature 302: 349–352
Cardoso de Almeida ML, Le Page RWF, Turner MJ (1984a) The release of variant surface glycoproteins of Trypanosoma brucei. In: August T (ed) Proceedings of the 3rd John Jacob Abel symposium on drug development: molecular parasitology
Cardoso de Almeida ML, Allan LM, Turner MJ (1984b) Purification and properties of the membrane form of variant surface glycoproteins (VSGs) from Trypanosoma brucei. J Protozool
Cross GAM (1975) Identification, purification and properties of clone-specific glycoprotein antigens constituting the surface coat of Trypanosoma brucei. Parasitology 71: 393–417
Cross GAM (1977) Isolation, structure and function of variant specific surface antigens. Ann Soc Belg Med Trop 57: 389–399
Cross GAM (1984) Structure of the variant glycoproteins and surface coat of Trypanosoma brucei. Proc R Soc Lond [Biol] 307: 3–12
Cross GAM, Johnson JG (1976) Structure and organisation of the variant specific antigens of Trypanosoma brucei. In: van den Bossche H (ed) Biochemistry of parasites and host-parasite relationships. North Holland Publishing, Amsterdam, pp 413–420
De Lange T, Liu AYC, Van der Ploeg LHT, Borst P, Tromp MC, Van Boom JH (1983) Tandem repetition of the 5′ mini-exon of variant surface glycoprotein genes: a multiple promoter for VSG gene transcription? Cell 34: 891–900
Diffley P, Strickler JE, Patton CL, Waksman BA (1980) Detection and quantitation of variant specific antigen in the plasma of rats and mice infected with Trypanosoma brucei. J Parasitol 66: 185–191
Doyle JJ, Hirumi H, Hirumi K, Lupton EN, Cross GAM (1980) Antigenic variation in clones of animal infective Trypanosoma brucei derived and cloned in vitro. Parasitology 80: 359–370
Duvillier G, Nouvelot A, Richet C, Baltz T, Degand P (1983) Presence of glycerol and fatty acids in the C-terminal end of a variant surface glycoprotein from Trypanosoma equiperdum. Biochem Biophys Res Commun 114: 119–125
Ferguson MAJ, Cross GAM (1984) Myristylation of the membrane form of a Trypanosoma brucei variant surface glycoprotein. J Biol Chem 259:
Gordon LM, Sauerheber RD, Esgate JA, Dipple I, Marchmont RJ, Houslay MD (1980) The increase in bilayer fluidity of rat liver plasma membranes achieved by the local anaesthetic benzyl alcohol affects the activity of intrinsic membrane enzymes. J Biol Chem 255: 4519–4527
Grab DJ, Ho S, Kara UAK, Rovis L (1984) Glycosyltransferase activities in Golgi and endoplasmic reticulum fractions isolated from African trypanosomes. J Cell Biol
Holder AA (1983a) Characterisation of the cross-reacting carbohydrate groups on two variant surface glycoproteins of Trypanosoma brucei. Mol Biochem Parasitol 7: 331–338
Holder AA (1983b) Carbohydrate is linked through ethanolamine to the C-terminal amino acid of Trypanosoma brucei variant surface glycoprotein. Biochem J 209: 261–262
Holder AA, Cross GAM (1981) Glycopeptides from variant surface glycoproteins of Trypanosoma brucei. C-terminal location of antigenically cross-reacting carbohydrate moieties. Mol Biochem Parasitol 2N: 135 - 150
Jackson DG (1983) Studies on the mechanism of release of the surface coat glycoprotein from Trypanosoma brucei. PhD Thesis, University of Dublin, Dublin
Jackson DG, Voorheis HP (1984) Studies on the mechanism of benzyl alcohol-stimulated release of the variant surface glycoprotein from Trypanosoma brucei. Eur J Biochem
Jackson DG, Owen MJ, Voorheis HP (1984) A new method for the rapid purification of both the membrane-bound and released forms of the surface coat protein from Trypanosoma brucei. Eur J Biochem
Jayawardena AN, Waksman BH (1977) Suppressor cells in experimental trypanosomiasis. Nature 265: 539–541
Kessler SW (1975) Rapid isolation of antigens from cells with a staphylococcal protein A-antibody adsorbant: parameters of the interaction of antibody-antigen complexes with protein A. J Immunol 115: 1617–1624
Kornfeld R, Kornfeld S (1980) The structure of glycoproteins and their oligosaccharide units. In: Lennarz W (ed) The biochemistry of glycoproteins and proteoglycans. Plenum, New York, pp 1–34
Krug RM, Broni BA, Boulay M (1979) Are the 5′ ends of influenza viral mRNAs synthesized in vivo donated by host mRNAs? Cell 18: 329–334
Lheureux M, Lheureux M, Vervoort T, Van Meirvenne N, Steinert M (1979) Immunological purification and partial characterisation of VSSA mRNA of T. brucei brucei. Nucleic Acids Res 7: 595–610
Lyon JA, Pratt JM, Travis RW, Doctor BP, Olenick JG (1981) Use of monoclonal antibody to immunochemically characterise variant specific surface coat protein from Trypanosoma b. rhodesiense. J Immunol 126: 134–137
Majumder HK, Boothroyd JC, Weber H (1981) Homologous 3′-terminal regions of mRNAs for surface antigens of different antigenic variants of Trypanosoma brucei. Nucleic Acids Res 9: 4745–4753
Matthyssens G, Michiels F, Hamers R, Pays E, Steinert M (1981) Two variant surface glycoproteins of Trypanosoma brucei have a conserved C-terminus. Nature 293: 230–233
McConnell J, Gurnett AM, Cordingley JS, Walker JE, Turner MJ (1981) Biosynthesis of Trypanosoma brucei variant surface glycoprotein. I. Synthesis, size and processing of an N-terminal signal peptide. Mol Biochem Parasitol 4: 225–242
McConnell J, Cordingley JS, Turner MJ (1982) The biosynthesis of Trypanosoma brucei variant surface glycoproteins — in vitro processing of signal peptide and glycosylation using heterologous rough endoplasmic reticulum vesicles. Mol Biochem Parasitol 6: 161–174
McConnell J, Turner MJ, Rovis L (1983) Biosynthesis of Trypanosoma brucei variant surface glycoproteins — analysis of carbohydrate heterogeneity and timing of post-transcriptional modifications. Mol Biochem Parasitol 8: 119–135
McGuire TC, Barbet AF, Hirumi H, Meshnick S, Doyle JJ (1980) Trypanosoma brucei: radioimmunoassay of variant surface glycoproteins from organisms grown in vitro and in vivo. Exp Parasitol 50: 233–239
Meyer DI, Dobberstein B (1980) A membrane component essential for vectorial translocation of nascent proteins across the endoplasmic reticulum. Requirements for its extraction and reassociation with membranes. J Cell Biol 87: 498–503
Meyer DI, Krause E, Dobberstein B (1982) Secretory protein translocation across membranes — the role of the docking protein. Nature 298: 647–650
Nelson RG, Parsons M, Barr PJ, Stuart K, Selkirk M, Agabian N (1983) Sequences homologous to the variant antigen mRNA spliced leader are located in tandem repeats and variable orphons in Trypanosoma brucei. Cell 34: 901: 909
Nelson RG, Parsons M, Selkirk M, Neuport G, Barr PJ, Agabian N (1984) Sequences homologous to variant antigen mRNA spliced leader in Trypanosomatidae which do not undergo antigenic variation. Nature 308: 665–667
O’Farrell C (1981) High resolution two-dimensional electrophoresis of proteins. J Biol Chem 250: 4007–4021
Olenick JG, Travis RW, Garson S (1981) Trypanosoma rhodesiense: chemical and immunological characterisation of variant specific surface coat glycoproteins. Mol Biochem Parasitol 3: 227–238
Opperdoes FR, Van Loy J (1982) The phospholipases of Trypanosoma brucei bloodstream forms and cultured procyclics. Mol Biochem Parasitol 5: 309–319
Overath P, Ozichos J, Stock V, Nonnengaesser C (1983) Repression of glycoprotein synthesis and release of surface coat during transformation of Trypanosoma brucei. EMBO J 2: 1721–1728
Ozaki LS, Svec P, Nussenzweig RS, Nussenzweig V, Godson G (1983) Structure of the Plasmodium knowlesi gene coding for the circumsporozoite protein. Cell 34: 815–822
Parodi AJ, Leloir LF (1979) The role of lipid intermediates on the glycosylation of proteins in the eucaryotic cell. Biochem Biophys Acta 559: 1–37
Parodi AJ, Allue LAQ, Cazzulo JJ (1981) Pathway of protein glycosylation in the trypanosomatid Crithidia fasciculata. Proc Natl Acad Sci USA 78: 6201–6205
Parsons M, Nelson RG, Stuart K, Agabian N (1984) Variant antigen genes of Trypanosoma brucei: genomic alteration of a spliced leader orphon and retention of expression-linked copies during differentiation. Proc Natl Acad Sci USA 81: 684–688
Pays E, Lheureux M, Steinert M (1982) Structure and expression of a Trypanosoma brucei gambiense variant specific antigen gene. Nucleic Acids Res 10: 3149–3163
Pays L, DeLauw MF, Van Assel S, Laurent M, Vervoort T, Van Meirvenne N, Steinert M (1983) Modifications of a Trypanosoma b. brucei antigen gene repertoire by different DNA recombinational mechanisms. Cell 35: 721–731
Pearson T, Anderson L (1980) Analytical techniques for cell fractions XXVIII. Dissection of complex antigenic mixtures using monoclonal antibodies and the two-dimensional gel electrophoresis. Anal Biochem 101: 377–386
Rautenberg P, Reinwald E, Risse H-J (1981) Sialic acids are responsible for charge heterogeneity of the variant surface glycoprotein of Trypanosoma congolense. Mol Biochem Parasitol 4: 129–138
Reinwald E, Risse H-J, Salker R (1978) Diazonitrobenzenesulphonate as a marker for cell surface proteins: study of the surface coat of Trypanosoma congolense. Physiol Chemie 359: 939–944
Reinwald E, Rautenberg P, Risse H-J (1979) Trypanosoma congolense: mechanical removal of the surface coat in vitro. Exp Parasitol 48: 384–397
Reinwald E, Rautenberg P, Risse H-J (1981) Purification of the variant antigens of Trypanosoma congolense. A new approach to the isolation of glycoproteins. Biochem Biophys Acta 668: 119–131
Rice-Ficht AC, Chen KK, Donelson JE (1981) Sequence homologies near the C-termini of the variable surface glycoproteins of Trypanosoma brucei. Nature 294: 53–57
Rovis C, Baekkeskov S (1980) Sub-cellular fractionation of Trypanosoma brucei. Isolation and characterisation of plasma membranes. Parasitology 80: 507–524
Rovis L, Dube DK (1981) Studies on the biosynthesis of variant surface glycoproteins of Trypanosoma brucei: sequence of glycosylation. Mol Biochem Parasitol 4: 77–93
Rovis L, Dube DK (1982) Identification and characterisation of two N-acetylglucosaminidases associated with Trypanosoma brucei microsomes. Mol Biochem Parasitol 5: 173–188
Seed JR (1964) Antigenic similarity among culture forms of the brucei group of trypanosomes. Parasitology 54: 593–596
Steiger R (1973) On the ultrastructure of Trypanosoma (Trypanozoon) brucei in the course of its life cycle, and some related aspects. Acta Trop 30: 64–68
Strickler JE, Patton CL (1980) Trypanosoma brucei brucei: inhibition of glycosylation of the major variable surface glycoprotein by tunicamycin. Proc Natl Acad Sci USA 77: 1529–1533
Strickler JE, Patton CL (1982a) Trypanosoma brucei: effct of inhibition of N-inked glycosylation on the nearest neighbour analysis of the major variable surface coat glycoprotein. Mol Biochem Parasitol 5: 117–132
Strickler JE, Patton CL (1982b) Trypanosoma brucei: nearest neighbour analysis on the major variable surface coat glycoprotein — cross-linking patterns with intact cells. Exp Parasitol 5: 117–132
Tizard I, Nielson KH, Seed JR, Hall JE (1978) Biologically active products from African trypanosomes. Microbiol Rev 42: 661–681
Turner MJ (1982a) Biochemistry of the variant surface glycoproteins of salivarian trypanosomes. Adv Parasitol 21: 69–153
Turner MJ (1982b) Antigenic variation in the trypanosome. Nature 298: 606–607
Turner MJ (1984) The biochemistry of variant surface glycoproteins of the African trypanosomes. In: Phelps C (ed) Molecular variants of proteins — biosynthesis and clinical relevance. Biochem Soc Symp
Van der Ploeg LHT (1984) Gene rearrangements controlling variant antigen expression in Trypanosoma brucei. Proc R Soc Lond [Biol] 307: 13–26
Van der Ploeg LHT, Liu AYC, Michels PAM, De Lange T, Borst P, Majumder HK, Weber H, Veeneman GH, Van Boom J (1982) RNA splicing is required to make the messenger RNA for a variant surface antigen in trypanosomes. Nucleic Acids Res 10: 3591–3604
Vickerman K (1969) On the surface coat and flagellar adhesion in trypanosomes. J Cell Sci 5: 163–193
Vickerman K, Barry JD (1982) African trypanosomes. In: Cohen S, Warren K (eds) Immunology of parasitic infections. Blackwell Scientific, Oxford, pp 204–260
Voorheis HP, Martin BR (1980) “Swell dialysis” demonstrated that adenylate cyclase in Trypanosoma brucei is regulated by calcium ions. Eur J Biochem 113:223–227
Voorheis HP, Martin BR (1981) Characteristics of the calcium-mediated mechanism activating adenylate cyclase in Trypanosoma brucei. Eur J Biochem 116: 471–477
Voorheis HP, Martin BR (1982) Local anaesthetics including benzyl alcohol activate the anedylate cyclase in Trypanosoma brucei by a calcium dependent mechanism. Eur J Biochem 123: 371–376
Voorheis HP, Gale JS, Owen MJ, Edwards W (1979) The isolation and partial characterization of the plasma membrane from Trypanosoma brucei. Biochem J 180: 11–24
Voorheis HP, Bowles DJ, Smith GA (1982) Characterisation of the release of the surface coat protein from bloodstream forms of Trypanosoma brucei. J Biol Chem 257: 2300–2304
Walter P, Blobel G (1982) Translocation of proteins across the endoplasmic reticulum. II. Signal recognition protein (SRP) mediates the selective binding to microsomal membranes of in vitro assembled polysomes synthesising secretory proteins. J Cell Biol 91: 551–557
Walter P, Ibrahami I, Blobel G (1982) Translocation of proteins across the endoplasmic reticulum. I. Signal recognition protein (SRP) binds to in vitro assembled polysomes synthesising secretory proteins. J Cell Biol 91: 545–550
Wright KA, Hales H (1970) Cytochemistry of the pellicle of bloodstream forms of Trypanosoma (Trypanozoon) brucei. J Parasitol 56: 671–683
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1985 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Turner, M.J., Cardoso de Almeida, M.L., Gurnett, A.M., Raper, J., Ward, J. (1985). Biosynthesis, Attachment and Release of Variant Surface Glycoproteins of the African Trypanosome. In: Hudson, L. (eds) The Biology of Trypanosomes. Current Topics in Microbiology and Immunology, vol 117. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-70538-0_2
Download citation
DOI: https://doi.org/10.1007/978-3-642-70538-0_2
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-70540-3
Online ISBN: 978-3-642-70538-0
eBook Packages: Springer Book Archive