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Structure and synthesis of nematode phosphorylcholine-containing glycoconjugates

Published online by Cambridge University Press:  18 November 2004

K. M. HOUSTON  and
W. HARNETT
K. M. HOUSTON
Affiliation:
The University of Strathclyde, Department of Immunology, Strathclyde Institute for Biomedical Sciences, 27 Taylor Street, Glasgow G4 0NR
W. HARNETT
Affiliation:
The University of Strathclyde, Department of Immunology, Strathclyde Institute for Biomedical Sciences, 27 Taylor Street, Glasgow G4 0NR
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Abstract

Infection with filarial nematodes produces a chronic, long-lasting illness with adult worms able to survive within human hosts for up to 15 years. A contributor to the longevity of these parasites is the presence of phosphorylcholine (PC) on components of the worms' molecular secretions (ES). PC on ES modulates host immune responses towards an anti-inflammatory phenotype thereby generating an environment favourable for parasite survival. PC is attached to nematode ES via a covalent association with carbohydrate, which, although well-documented in bacteria and fungi, is absent from humans, making it an ideal target for the development of novel drugs. In order to produce such drugs it is first necessary to understand the structure and synthesis of nematode PC-glycans. ES-62 is the major PC-ES-product of Acanthocheilonema viteae and is a homologue of PC-ES found in human filarial nematodes. We have studied the structure and biosynthesis of PC-glycans of ES-62 by a combination of pulse-chase experiments, experiments involving the use of inhibitors of each of intracellular trafficking, oligosaccharide processing and phospholipid biosynthesis and various forms of mass spectrometry. Our indications indicate that PC is transferred in the lumen of the medial Golgi to an N-type glycan consisting of a trimannosyl core with or without core fucosylation bearing between 1 and 4 N-acetyl glucosamine residues. The structure of the PC-N-glycans found in ES-62 appears to be conserved amongst filarial nematodes in that it has additionally been identified in Onchocerca volvulus and O. gibsoni. Also, similar structures have been found in non-filarial parasitic nematodes and in the free-living nematode Caenorhabditis elegans. Finally, PC has also been recently found attached to the carbohydrate moieties of nematode glycosphingolipids and the structure of these will also be considered.

Keywords

glycoconjugatesnematodephosphorylcholine
Type
Review Article
Information
Parasitology , Volume 129 , Issue 6 , December 2004 , pp. 655 - 661
Copyright
© 2004 Cambridge University Press

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References

REFERENCES

ALLAN, D. & OBRADORS, M. J. M. ( 1999). Enzyme distributions in subcellular fractions of BHK cells infected with Semliki virus: evidence for major fraction of sphingomyelin synthase in the trans-golgi network. Biochimica et Biophysica Acta 1450, 277–287.CrossRefGoogle Scholar
BISHOP, W. R. & BELL, R. M. ( 1988). Assembly of phospholipids into cellular membranes: biosynthesis, transmembrane movement and intracellular translocation. Annual Review of Cell Biology 4, 579–610.CrossRefGoogle Scholar
CARMAN, G. M. & HENRY, S. A. ( 1989). Phospholipid biosynthesis in yeast. Annual Review of Biochemistry 58, 6635–6669.CrossRefGoogle Scholar
CARMAN, G. M. & HENRY, S. A. ( 1999). Phospholipid biosynthesis in the yeast Saccharomyces cerevisiae and interrelationship with other metabolic processes. Progress in Lipid Research 38, 361–399.CrossRefGoogle Scholar
CARROLL, M. & BIRD, M. M. ( 1991). Glycoprotein expression in mouse cerebellum: effects of inhibitors of N-linked glycosylation. International Journal of Biochemistry 23, 1285–1291.CrossRefGoogle Scholar
CIPOLLO, J. F., COSTELLO, C. E. & HIRSCHBERG, C. B. ( 2002). The fine structure of Caenorhabditis elegans N-glycans. Journal of Biological Chemistry 277, 49143–49157.CrossRefGoogle Scholar
ELBEIN, A. D. ( 1987). Inhibitors of the biosynthesis and processing of N-linked oligosaccharide chains. Annual Review of Biochemistry 56, 497–534.CrossRefGoogle Scholar
ELBEIN, A. D., TROPEA, J. E., MITCHELL, M. & KAUSHAL, G. P. ( 1990). Kufunensine, a potent inhibitor of the glycoprotein processing mannosidase I. Journal of Biological Chemistry 265, 15599–15605.Google Scholar
GERDT, S., DENNIS, R. D., BORGONIE, G., SCHNABEL, R. & GEYER, R. ( 1999). Isolation, characterization and immunolocalization of phosphorylcholine-substituted glycolipids in developmental stages of Caenorhabditis elegans. European Journal of Biochemistry 266, 952–963.CrossRefGoogle Scholar
HARNETT, W., FRAME, M. J., NOR, Z. M., MACDONALD, M. & HOUSTON, K. M. ( 1994). Some preliminary data on the nature/structure of the PC-glycan of the major excretory–secretory product of Acanthocheilonema viteae (ES-62). Parasite 1, 179–181.CrossRefGoogle Scholar
HARNETT, W., HOUSTON, K. M., AMESS, R. & WORMS, M. J. ( 1993). Acanthocheilonema viteae: phosphorylcholine is attached to the major excretory–secretory product via an N-linked glycan. Experimental Parasitology 77, 498–502.CrossRefGoogle Scholar
HARNETT, W., WORMS, M. J., KAPIL, A., GRAINGER, M. & PARKHOUSE, R. M. ( 1989). Origin, kinetics of circulation and fate in vivo of the major excretory–secretory product of Acanthocheilonema viteae. Parasitology 99, 229–239.CrossRefGoogle Scholar
HASLAM, S. M. & DELL, A. ( 2003). Hallmarks of Caenorhabditis elegans N-glycosylation: complexity and controversy. Biochimie 85, 25–32.CrossRefGoogle Scholar
HASLAM, S. D., GEMS, D., MORRIS, H. R. & DELL, A. ( 2002). The glycomes of Caenorhabditis elegans and other model organisms. Biochemical Society Symposium 69, 117–134.CrossRefGoogle Scholar
HASLAM, S. M., HOUSTON, K. M., HARNETT, W., REASON, A. J., MORRIS, H. R. & DELL, A. ( 1999). Structural studies of N-glycans of filarial parasites. Conservation of phosphorylcholine-substituted glycans among species and discovery of novel chito-oligomers. Journal of Biological Chemistry 274, 20953–20960.Google Scholar
HASLAM, S. M., KHOO, K. H., HOUSTON, K. M., HARNETT, W., MORRIS, H. R. & DELL, A. ( 1997). Characterisation of the phosphorylcholine-containing N-linked oligosaccharides in the excretory–secretory 62 kDa glycoprotein of Acanthocheilonema viteae. Molecular and Biochemical Parasitology 85, 53–66.CrossRefGoogle Scholar
HOUSTON, K. M., CUSHLEY, W. & HARNETT, W. ( 1997). Studies on the site and mechanism of attachment of phosphorylcholine to a filarial nematode secreted glycoprotein. Journal of Biological Chemistry 272, 1527–1533.CrossRefGoogle Scholar
HOUSTON, K. M. & HARNETT, W. ( 1996). Prevention of attachment of phosphorylcholine to a major excretory–secretory product of Acanthocheilonema viteae using tunicamycin. Journal of Parasitology 82, 320–324.CrossRefGoogle Scholar
HOUSTON, K. M. & HARNETT, W. ( 1999). Mechanisms underlying the transfer of phosphorylcholine to filarial nematode glycoproteins – a possible role for choline kinase. Parasitology 118, 311–318.CrossRefGoogle Scholar
HOUSTON, K. M., LOCHNIT, G., GEYER, R. & HARNETT, W. ( 2002). Investigation of the nature of potential phosphorylcholine donors for filarial nematode glycoconjugates. Molecular and Biochemical Parasitology 123, 55–66.CrossRefGoogle Scholar
HUNZIKER, W., WHITNEY, J. A. & MELLMAN, I. ( 1992). Brefeldin A and the endocytic pathway. Possible implications for membrane traffic and sorting. FEBS Letters 307, 93–96.Google Scholar
KAMINSKY, R. ( 2003). Drug resistance in nematodes: a paper tiger or a real problem? Current Opinion in Infectious Diseases 16, 559–564.Google Scholar
LAL, R. B., PARANJAPE, R. S., BRILES, D. E., NUTMAN, T. B. & OTTESEN, E. A. ( 1987). Circulating parasite antigen(s) in lymphatic filariasis: use of monoclonal antibodies to phosphocholine for immunodiagnosis. Journal of Immunology 138, 3454–3460.Google Scholar
LODISH, H. F. & KONG, N. ( 1984). Glucose removal from N-linked oligosaccharides is required for efficient maturation of certain secretory glycoproteins from the rough endoplasmic reticulum to the Golgi complex. Journal of Cell Biology 98, 1720–1729.CrossRefGoogle Scholar
LOCHNIT, G., DENNIS, R. D., ULMER, A. J. & GEYER, R. ( 1998). Structural elucidation and monokine-inducing activity of two biologically active zwitterionic glycosphingolipids derived from the parasitic nematode Ascaris suum. Journal of Biological Chemistry 278, 466–474.CrossRefGoogle Scholar
MAIZELS, R. M., BURKE, J. & DENHAM, D. A. ( 1987). Phosphorylcholine-bearing antigens in filarial nematode parasites: analysis of somatic extracts, in-vitro secretions and infection sera from Brugia malayi and B. pahangi. Parasite Immunology 9, 49–66.CrossRefGoogle Scholar
MIQUEL, K., PRADINES, A., TERCE, F., SELMI, S. & FAVRE, G. ( 1998). Competitive inhibition of choline phosphotransferase by geranylgeraniol and farnesol inhibits phosphatidylcholine synthesis and induces apoptosis in human lung adenocarcinoma A549 cells. Jorunal of Biological Chemistry 273, 26179–26186.CrossRefGoogle Scholar
MORELLE, W., HASLAM, S. M., MORRIS, H. R. & DELL, A. ( 2000 a). Characterization of the N-linked glycans of adult Trichinella spiralis. Molecular and Biochemical Parasitology 109, 171–177.Google Scholar
MORELLE, W., HASLAM, S. M., OLIVIER, V., APPLETON, J. A., MORRIS, H. R. & DELL, A. ( 2000 b). Phosphorylcholine-containing N-glycans of Trichinella spiralis: identification of multiantennary lacdiNAc structures. Glycobiology 10, 941–950.Google Scholar
NOR, Z. M., DEVANEY, E. & HARNETT, W. ( 1997). The use of inhibitors of N-linked glycosylation and oligosaccharide processing to produce monoclonal antibodies against non-phosphorylcholine epitopes of Brugia pahangi excretory–secretory products. Parasitology Research 83, 813–815.CrossRefGoogle Scholar
NOR, Z. M., HOUSTON, K. M., DEVANEY, E. & HARNETT, W. ( 1997). Variation in the nature of attachment of phosphorylcholine to excretory–secretory products of adult Brugia pahangi. Parasitology 114, 257–262.CrossRefGoogle Scholar
PERY, P., PETIT, A., POULAIN, J. & LUFFAU, G. ( 1974). Phosphorylcholine-bearing components in homogenates of nematodes. European Journal of Immunology 4, 637–639.CrossRefGoogle Scholar
PFEFFER, S. R. & ROTHMAN, J. E. ( 1987). Biosynthetic protein transport and sorting by the endoplasmic reticulum and Golgi. Annual Review of Biochemistry 56, 829–852.CrossRefGoogle Scholar
STEPEK, G., AUCHIE, M., TATE, R., WATSON, K., RUSSELL, D. G., DEVANEY, E. & HARNETT, W. ( 2002). Expression of the filarial nematode phosphorylcholine-containing glycoprotein, ES62, is stage specific. Parasitology 125, 155–164.CrossRefGoogle Scholar
VANCE, D. E., TRIPP, E. M. & PADDON, H. B. ( 1980). Poliovirus increases phosphatidylcholine biosynthesis in HeLa cells by stimulation of the rate-limiting reaction catalyzed by CTP: phosphocholine cytidylyltransferase. Journal of Biological Chemistry 255, 1064–1069.Google Scholar
WALLER, P. J. ( 1997). Anthelmintic resistance. Veterinary Parasitology 72, 391–405.CrossRefGoogle Scholar
WORLD HEALTH ORGANIZATION ( 1997). Prospects for the elimination of some TDR diseases. World Health Organization, Geneva.
WUHRER, M., RICKHOFF, S., DENNIS, R. D., LOCHNIT, G., SOBOSLAY, P. T., BAUMEISTER, S. & GEYER, R. ( 2000). Phosphocholine-containing zwitterionic glycosphingolipids of adult Onchocerca volvulus as highly conserved antigenic structures of parasitic nematodes. The Biochemical Journal 348, 417–423.CrossRefGoogle Scholar