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Biochemistry and molecular genetics of Leishmania glucose transporters

Published online by Cambridge University Press:  06 April 2009

C. K. Langford ,
R. J. S. Burchmore ,
D. T. Hart ,
W. Wagner  and
S. M. Landfear
C. K. Langford
Affiliation:
Department of Microbiology and Immunology, Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Road, Portland, Oregon 97201, U.S.A.
R. J. S. Burchmore
Affiliation:
Division of Life Sciences, King's College London, Campden Hill Road, London W8 7AH, U.K.
D. T. Hart
Affiliation:
Division of Life Sciences, King's College London, Campden Hill Road, London W8 7AH, U.K.
W. Wagner
Affiliation:
Department of Microbiology and Immunology, Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Road, Portland, Oregon 97201, U.S.A.
S. M. Landfear*
Affiliation:
Department of Microbiology and Immunology, Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Road, Portland, Oregon 97201, U.S.A.
*
* Corresponding author.
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Summary

Glucose is utilized as a significant source of metabolic energy by Leishmania parasites. This sugar is accumulated by the parasite via a specific carrier-mediated transport system located in the parasite membrane. Parasites may also contain another transporter that shuttles glucose between the cytoplasm and the glycosome, a membrane-bound organelle where the early steps of glycolysis occur. The transport systems of both the insect stage promastigotes and the intracellular amastigotes have been characterized and shown to have kinetic properties that are consistent with the different physio-logical environments of the insect gut and the macrophage phagolysosome. Several genes have been cloned from Leishmania species which encode proteins with substantial sequence similarity to glucose transporters from mammals and lower eukaryotes. Two of these genes are expressed preferentially in the promastigote stage of the life cycle, where glucose is more readily available and more rapidly transported and metabolized than in the intracellular amastigotes. One of these two developmentally-regulated genes has been functionally expressed in Xenopus oocytes and shown to encode a glucose transporter. A third gene encodes a protein that is also a member of the glucose transporter family on the basis of sequence similarity and proposed secondary structure. However, the significant differences between this protein and the other two suggest that it is likely to transport a different substrate. Functional expression will be required to define the specific biochemical role of each gene within the parasite.

Keywords

glucose transporterLeishmaniamembrane proteinsgene cloning.
Type
Research Article
Information
Parasitology , Volume 108 , supplement S1: Symposia of the British Society for Parasitology Volume 31:Functional molecules on the surface of protozoan parasites , March 1994 , pp. S73 - S83
Copyright
Copyright © Cambridge University Press 1994

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References

REFERENCES

Baldwin, S. A. (1992). Mechanisms of active and passive transport in a family of homologous sugar transporters found in both prokaryotes and eukaryotes. In Molecular Aspects of Transport Proteins (ed. De, Pont), pp. 169—217. Amsterdam: Elsevier Science Publishers.Google Scholar
Baldwin, S. A. & Henderson, P. J. F. (1989). HomologieS between sugar transporters from eukaryotes and prokaryotes. Annual Reviews in Physiology 51, 459–71.CrossRefGoogle ScholarPubMed
Baly, D. L. & Horuk, R. (1988). The biology and biochemistry of the glucose transporter. Biochimica et Biophysica Acta 947, 571–90.CrossRefGoogle ScholarPubMed
Blum, J. J. (1993). Intermediary metabolism of Leishmania. Parasitology Today 9, 118—22.CrossRefGoogle ScholarPubMed
Bringaud, F. & Baltz, T. (1992). A potential hexose transporter gene expressed predominantly in the bloodstream form of Trypanosoma brucei. Molecular and Biochemical Parasitology 52, 111–22.CrossRefGoogle ScholarPubMed
Bringaud, F. & Baltz, T. (1993). Differential regulation of two distinct families of glucose transporter genes in Trypanosoma brucei. Molecular and Cell Biology 13, 1146–54.Google ScholarPubMed
Burchmore, J. S. & Hart, D. T. (submitted). Glucose transport in promastigotes and amastigotes of Leishmania mexicana: characterization and comparison with host glucose transporters.Google Scholar
Cairns, B. R., Collard, M. W. & Landfear, S. M. (1989). Developmentally regulated gene from Leishmania encodes a putative membrane transport protein. Proceedings of the National Academy of Sciences, U.S.A. 86, 7682–6.CrossRefGoogle ScholarPubMed
Cazzulo, J. J. (1992). Aerobic fermentation of glucose by trypanosomatids. FASEB Journal 6, 3153–61.CrossRefGoogle ScholarPubMed
Celenza, J. L., Marshall-Carlson, L. & Carlson, M. (1988). The yeast SNF3 gene encodes a glucose transporter homologous to the mammalian protein. Proceedings of the National Academy of Sciences, U.S.A. 85, 2130–4.CrossRefGoogle Scholar
Coombs, G. H., Craft, J. A. & Hart, D. T. (1982). A comparative study of Leishmania mexicana amastigotes and promastigotes. Enzyme activities and subcellular locations. Molecular and Biochemical Parasitology 5, 199–211.CrossRefGoogle ScholarPubMed
Coppens, I., Baudhuin, P., Opperdoes, F. R. & Courtoy, P. J. (1988). Receptors for the host low density lipoproteins of the hemoflagellate Trypanosoma brucei: purification and involvement in the growth of the parasite. Proceedings of the National Academy of Sciences, U.S.A. 85, 6753–7.CrossRefGoogle ScholarPubMed
Cruz, A., Coburn, C. M. & Beverley, S. M. (1991). Double targeted gene replacement for creating null mutants. Proceedings of the National Academy of Sciences, U.S.A. 88, 7170–4.CrossRefGoogle ScholarPubMed
de Lafaille, Curotto M. A. & Wirth, D. F. (1992). Creation of null/ + mutants of the α-tubulin gene in Leishmania enriettii by gene cluster deletion. Journal of Biological Chemistry 267, 23839–46.CrossRefGoogle Scholar
Davies, A., Meeran, K., Cairns, M. T. & Baldwin, S. (1987). Peptide-specific antibodies as probes of the orientation of the glucose transporter in the human erythrocyte membrane. Journal of Biological Chemistry 262, 9347–52.CrossRefGoogle ScholarPubMed
Eisenberg, D., Schwarz, E., Komaromy, M. & Wall, R. (1984). Analysis of membrane and surface protein sequences with a hydrophobic moment plot. Journal of Molecular Biology 179, 125–42.CrossRefGoogle ScholarPubMed
Eisenthal, R., Game, S. & Holman, G. D. (1988). Specificity of hexose transport in Trypanosoma brucei. Biochimica et Biophysica Acta 985, 81–9.CrossRefGoogle Scholar
Feinberg, A. P. & Vogelstein, B. (1983). A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Analytical Biochemistry 132, 6–13.CrossRefGoogle ScholarPubMed
Gould, G. W. & Bell, G. I. (1990). Facilitative glucose transporters: an expanding family. Trends in Biochemical Sciences 15, 18–23.CrossRefGoogle ScholarPubMed
Hart, D. T. & Coombs, G. H. (1982). Leishmania mexicana: energy metabolism of amastigotes and promastigotes. Experimental Parasitology 54, 397–409.CrossRefGoogle Scholar
Hart, D. T. & Opperdoes, F. R. (1984). The occurrence of glycosomes (microbodies) in the promastigote stage of four major Leishmania species. Molecular and Biochemical Parasitology 13, 159–72.CrossRefGoogle ScholarPubMed
Haspel, H. C., Rosenfeld, M. G. & Rosen, O. M. (1988). Characterization of antisera to a synthetic carboxylterminal peptide of the glucose transporter protein. Journal of Biological Chemistry 262, 398–403.CrossRefGoogle Scholar
Hediger, M. A., Coady, M. J., Ikeda, T. S. & Wright, E. M. (1987). Expression cloning and cDNA sequencing of the Na+/glucose co-transporter. Nature 330, 379–81.CrossRefGoogle ScholarPubMed
Iovannisci, D. M. & Ullman, B. (1983). High efficiency plating method for Leishmania promastigotes in semidefined or completely-defined medium. Journal of Parasitology 69, 633–6.CrossRefGoogle ScholarPubMed
Keegan, F. P. & Blum, J. J. (1992). Utilization of a carbohydrate reserve comprised primarily of mannose by Leishmania donovani. Molecular and Biochemical Parasitology 53, 193–200.CrossRefGoogle ScholarPubMed
Kolodziej, P. A. & Young, R. A. (1991). Epitope tagging and protein surveillance. Methods in Enzymology 194, 508–19.CrossRefGoogle ScholarPubMed
Langford, C. K., Ewbank, S. A., Hanson, S. A., Ullman, B. & Landfear, S. M. (1992). Molecular characterization of two genes encoding members of the glucose transporter superfamily in the parasitic protozoan Leishmania donovani. Molecular and Biochemical Parasitology 55, 51–64.CrossRefGoogle ScholarPubMed
Lee, M. G.-S., Bihain, B. E., Russell, D. G., Deckelbaum, R. J. & Van Der Ploeg, L. H. T. (1990). Characterization of a cDNA encoding a cysteine-rich cell surface protein located in the flagellar pocket of the protozoan Trypanosoma brucei. Molecular and Cellular Biology 10, 4506–17.CrossRefGoogle ScholarPubMed
Maiden, M. C. J., Davis, E. O., Baldwin, S. A., Moore, D. C. M. & Henderson, P. J. F. (1987). Mammalian and bacterial sugar transport proteins are homologous. Nature 325, 641–3.CrossRefGoogle ScholarPubMed
Mueckler, M., Caruso, C., Baldwin, S. A., Panico, M., Blench, I., Morris, H. R., Allard, W. J., Lienhard, G. E. & Lodish, H. F. (1985). Sequence and structure of a human glucose transporter. Science 229, 941–5.CrossRefGoogle ScholarPubMed
Munoz-Antonia, T., Richards, F. F. & Ullu, E. (1991). Differences in glucose transport between bloodstream and procyclic forms of Trypanosoma brucei rhodesiense. Molecular and Biochemical Parasitology 47, 73–82.CrossRefGoogle ScholarPubMed
Opperdoes, F. R. (1991). Glycosomes. In Biochemical Protozoology (ed. Coombs, G. & North, M.), pp. 134–144. London and Washington: Taylor and Francis.Google Scholar
Parsons, M. & Nielsen, B. (1990). Active transport of 2-deoxy-D-glucose in Trypanosoma brucei. Molecular and Biochemical Parasitology 42, 197–204.CrossRefGoogle ScholarPubMed
Pastakia, K. B. & Dwyer, D. M. (1987). Identification and characterization of a ribose transport system in Leishmania donovani promastigotes. Molecular and Biochemical Parasitology 26, 175–82.CrossRefGoogle ScholarPubMed
Piper, R. C., Tai, C., Slot, J. W., Hahn, C. S., Rice, D., Huang, H. & James, D. E. (1992). The efficient intracellular sequestration of the insulin-regulatable glucose transporter (GLUT4) is conferred by the N terminus. Journal of Cellular Biology 117, 729–43.CrossRefGoogle Scholar
Saiki, R. K., Gelfand, D. H., Stoffel, S., Scharf, S., Higuchi, R., HorN, G. T., Mullis, K. B. & Erlich, H. A.(1988). Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239, 487–91.CrossRefGoogle ScholarPubMed
Schaefer, F. W. & Mukkada, A. J. (1976). Specificity of the glucose transport system in Leishmania tropica promastigotes. Journal of Protozoology 23, 446–9.CrossRefGoogle ScholarPubMed
Schlein, Y. (1986). Sandfly diet and Leishmania. Parasitology Today 2, 175–7.CrossRefGoogle ScholarPubMed
Seyfang, A. & Duszenko, M. (1991). Specificity of glucose transport in Trypanosoma brucei: effective inhibition by phloretin and cytochalasin B. European Journal of Biochemistry 202, 191–6.CrossRefGoogle ScholarPubMed
Silverman, M. (1991). Structure and function of hexose transporters. Annual Reviews of Biochemistry 60, 757–94.CrossRefGoogle ScholarPubMed
Slot, J. N. W., Geuze, H. J., Gigengack, S., James, D. E. & Leinhard, G. E. (1991). Translocation of the glucose transporter GLUT4 in cardiac myocytes of the rat. Proceedings of the National Academy of Sciences, U.S.A. 88, 7815–9.CrossRefGoogle ScholarPubMed
Stack, S. P., Stein, D. R. & Landfear, S. M. (1990). Structural isoforms of a membrane transport protein from Leishmania. Molecular and Cellular Biology 10, 6785–90.Google ScholarPubMed
Stein, D. R., Cairns, B. R. & Landfear, S. M. (1990). Developmentally regulated transporter in Leishmania is encoded by a family of clustered genes. Nucleic Acids Research 18, 1549–57.CrossRefGoogle ScholarPubMed
Kuile, Ter B. H. (1993). Glucose and proline transport in kinetoplastids. Parasitology Today 9, 206–10.CrossRefGoogle Scholar
Kuile, Ter B. H. & Opperdoes, F. R. (1992). Comparative physiology of two protozoan parasites, Leishmania donovani and Trypanosoma brucei, grown in chemostats. Journal of Bacteriology 174, 2929–34.CrossRefGoogle ScholarPubMed
Thorens, B., Charron, M. J. & Lodish., H. F. (1990). Molecular physiology of glucose transporters. Diabetes Care 13, 209–18.CrossRefGoogle ScholarPubMed
Wadzinski, B. E., Shanahan, M. F. & Ruoho, A. E. (1987). Derivatization of the human erythrocyte glucose transporter using a novel forskolin photoaffinity label. Journal of Biological Chemistry 262, 17683–9.CrossRefGoogle ScholarPubMed
Walmsley, A. R. (1988). The dynamics of the glucose transporter. Trends in Biochemical Science 12, 226–31.CrossRefGoogle Scholar
Warburg, A. & Schlein, Y. (1986). The effect of post-bloodmeal nutrition of Phlebotomus papatasi on the transmission of Leishmania major. American Journal of Tropical Medicine and Hygiene 35, 926–30.CrossRefGoogle ScholarPubMed
Zilberstein, D. & Dwyer, D. (1984). Glucose transport in Leishmania donovani promastigotes. Molecular and Biochemical Parasitology 12, 327—36.CrossRefGoogle ScholarPubMed
Zilberstein, D. & Dwyer, D. (1985). Proton force-driven active transport of D-glucose and L-proline in the protozoan parasite Leishmania donovani. Proceedings of the National Academy of Sciences, U.S.A. 82, 1716–20.CrossRefGoogle ScholarPubMed
Zilberstein, D., Dwyer, D. M., Matthaei, S. & Horuk, R. (1986). Identification and biochemical characterization of the plasma membrane glucose transporter of Leishmania donovani. Journal of Biological Chemistry 261, 15053–7.CrossRefGoogle ScholarPubMed