Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 29 September 1995:
Vol. 269. no. 5232, pp. 1869 - 1872
DOI: 10.1126/science.7569927

Articles

Science, Vol 269, Issue 5232, 1869-1872
Copyright © 1995 by American Association for the Advancement of Science


articles

A specialized pathway affecting virulence glycoconjugates of Leishmania

A Descoteaux, Y Luo, SJ Turco, and SM Beverley

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.

For virulence and transmission, the protozoan parasite Leishmania must assemble a complex glycolipid on the cell surface, the lipophosphoglycan (LPG). Functional complementation identified the gene LPG2, which encodes an integral Golgi membrane protein implicated in intracellular compartmentalization of LPG biosynthesis. Ipg2- mutants lack only characteristic disaccharide-phosphate repeats, normally present on both LPG and other surface or secreted molecules considered critical for infectivity. In contrast, a related yeast gene, VAN2/VRG4, is essential and required for general Golgi function. These results suggest that LPG2 participates in a specialized virulence pathway, which may offer an attractive target for chemotherapy.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Two Functionally Divergent UDP-Gal Nucleotide Sugar Transporters Participate in Phosphoglycan Synthesis in Leishmania major.
A. A. Capul, T. Barron, D. E. Dobson, S. J. Turco, and S. M. Beverley (2007)
J. Biol. Chem. 282, 14006-14017
   Abstract »    Full Text »    PDF »
Endosome Sorting and Autophagy Are Essential for Differentiation and Virulence of Leishmania major.
S. Besteiro, R. A. M. Williams, L. S. Morrison, G. H. Coombs, and J. C. Mottram (2006)
J. Biol. Chem. 281, 11384-11396
   Abstract »    Full Text »    PDF »
Functional expression of the CMP-sialic acid transporter in Escherichia coli and its identification as a simple mobile carrier.
J. Tiralongo, A. Ashikov, F. Routier, M. Eckhardt, H. Bakker, R. Gerardy-Schahn, and M. von Itzstein (2006)
Glycobiology 16, 73-81
   Abstract »    Full Text »    PDF »
Trichomonas vaginalis Lipophosphoglycan Mutants Have Reduced Adherence and Cytotoxicity to Human Ectocervical Cells.
F. D. Bastida-Corcuera, C. Y. Okumura, A. Colocoussi, and P. J. Johnson (2005)
Eukaryot. Cell 4, 1951-1958
   Abstract »    Full Text »    PDF »
Reconstitution of GDP-mannose Transport Activity with Purified Leishmania LPG2 Protein in Liposomes.
H. Segawa, R. P. Soares, M. Kawakita, S. M. Beverley, and S. J. Turco (2005)
J. Biol. Chem. 280, 2028-2035
   Abstract »    Full Text »    PDF »
Characterization of a Defensin from the Sand Fly Phlebotomus duboscqi Induced by Challenge with Bacteria or the Protozoan Parasite Leishmania major.
N. Boulanger, C. Lowenberger, P. Volf, R. Ursic, L. Sigutova, L. Sabatier, M. Svobodova, S. M. Beverley, G. Spath, R. Brun, et al. (2004)
Infect. Immun. 72, 7140-7146
   Abstract »    Full Text »    PDF »
Vaccination with Phosphoglycan-Deficient Leishmania major Protects Highly Susceptible Mice from Virulent Challenge without Inducing a Strong Th1 Response.
J. E. Uzonna, G. F. Spath, S. M. Beverley, and P. Scott (2004)
J. Immunol. 172, 3793-3797
   Abstract »    Full Text »    PDF »
Persistence Without Pathology in Phosphoglycan-Deficient Leishmania major.
G. F. Spath, L.-F. Lye, H. Segawa, D. L. Sacks, S. J. Turco, and S. M. Beverley (2003)
Science 301, 1241-1243
   Abstract »    Full Text »    PDF »
Identification of Genes Encoding Arabinosyltransferases (SCA) Mediating Developmental Modifications of Lipophosphoglycan Required for Sand Fly Transmission of Leishmania major.
D. E. Dobson, B. J. Mengeling, S. Cilmi, S. Hickerson, S. J. Turco, and S. M. Beverley (2003)
J. Biol. Chem. 278, 28840-28848
   Abstract »    Full Text »    PDF »
Functional Identification of Galactosyltransferases (SCGs) Required for Species-specific Modifications of the Lipophosphoglycan Adhesin Controlling Leishmania major-Sand Fly Interactions.
D. E. Dobson, L. D. Scholtes, K. E. Valdez, D. R. Sullivan, B. J. Mengeling, S. Cilmi, S. J. Turco, and S. M. Beverley (2003)
J. Biol. Chem. 278, 15523-15531
   Abstract »    Full Text »    PDF »
Transport of UDP-galactose in Plants. IDENTIFICATION AND FUNCTIONAL CHARACTERIZATION OF AtUTr1, AN ARABIDOPSIS THALIANA UDP-GALACTOSE/UDP-GLUCOSE TRANSPORTER.
L. Norambuena, L. Marchant, P. Berninsone, C. B. Hirschberg, H. Silva, and A. Orellana (2002)
J. Biol. Chem. 277, 32923-32929
   Abstract »    Full Text »    PDF »
Identification of a Disulfide Isomerase Protein of Leishmania major as a Putative Virulence Factor.
Y. B. Achour, M. Chenik, H. Louzir, and K. Dellagi (2002)
Infect. Immun. 70, 3576-3585
   Abstract »    Full Text »    PDF »
Molecular and Phenotypic Analysis of CaVRG4, Encoding an Essential Golgi Apparatus GDP-Mannose Transporter.
A. Nishikawa, J. B. Poster, Y. Jigami, and N. Dean (2002)
J. Bacteriol. 184, 29-42
   Abstract »    Full Text »    PDF »
Identification and Characterization of GONST1, a Golgi-Localized GDP-Mannose Transporter in Arabidopsis.
T. C. Baldwin, M. G. Handford, M.-I. Yuseff, A. Orellana, and P. Dupree (2001)
PLANT CELL 13, 2283-2295
   Abstract »    Full Text »    PDF »
The role of phosphoglycans in Leishmania-sand fly interactions.
D. L. Sacks, G. Modi, E. Rowton, G. Spath, L. Epstein, S. J. Turco, and S. M. Beverley (2000)
PNAS 97, 406-411
   Abstract »    Full Text »    PDF »
Isolation of Genes Mediating Resistance to Inhibitors of Nucleoside and Ergosterol Metabolism in Leishmania by Overexpression/Selection.
P. C. Cotrim, L. K. Garrity, and S. M. Beverley (1999)
J. Biol. Chem. 274, 37723-37730
   Abstract »    Full Text »    PDF »
Reconstitution, Identification, and Purification of the Rat Liver Golgi Membrane GDP-fucose Transporter.
L. Puglielli and C. B. Hirschberg (1999)
J. Biol. Chem. 274, 35596-35600
   Abstract »    Full Text »    PDF »
Role of Protein Kinase C-{alpha} in the Control of Infection by Intracellular Pathogens in Macrophages.
A. St-Denis, V. Caouras, F. Gervais, and A. Descoteaux (1999)
J. Immunol. 163, 5505-5511
   Abstract »    Full Text »    PDF »
A New Type of Carbohydrate-deficient Glycoprotein Syndrome Due to a Decreased Import of GDP-fucose into the Golgi.
T. Lubke, T. Marquardt, K. von Figura, and C. Korner (1999)
J. Biol. Chem. 274, 25986-25989
   Abstract »    Full Text »    PDF »
Membrane Topology of the Mammalian CMP-Sialic Acid Transporter.
M. Eckhardt, B. Gotza, and R. Gerardy-Schahn (1999)
J. Biol. Chem. 274, 8779-8787
   Abstract »    Full Text »    PDF »
Identification and Purification of the Rat Liver Golgi Membrane UDP-N-acetylgalactosamine Transporter.
L. Puglielli, E. C. Mandon, D. M. Rancour, A. K. Menon, and C. B. Hirschberg (1999)
J. Biol. Chem. 274, 4474-4479
   Abstract »    Full Text »    PDF »
Three proteins involved in Caenorhabditis elegans vulval invagination are similar to components of a glycosylation pathway.
T. Herman and H. R. Horvitz (1999)
PNAS 96, 974-979
   Abstract »    Full Text »    PDF »
Cloning of Leishmania nucleoside transporter genes by rescue of a transport-deficient mutant.
G. Vasudevan, N. S. Carter, M. E. Drew, S. M. Beverley, M. A. Sanchez, A. Seyfang, B. Ullman, and S. M. Landfear (1998)
PNAS 95, 9873-9878
   Abstract »    Full Text »    PDF »
Mutants of the CMP-sialic Acid Transporter Causing the Lec2 Phenotype.
M. Eckhardt, B. Gotza, and R. Gerardy-Schahn (1998)
J. Biol. Chem. 273, 20189-20195
   Abstract »    Full Text »    PDF »
Stage-specific Proteophosphoglycan from Leishmania mexicana Amastigotes. STRUCTURAL CHARACTERIZATION OF NOVEL MONO-, DI-, AND TRIPHOSPHORYLATED PHOSPHODIESTER-LINKED OLIGOSACCHARIDES.
T. Ilg, D. Craik, G. Currie, G. Multhaup, and A. Bacic (1998)
J. Biol. Chem. 273, 13509-13523
   Abstract »    Full Text »    PDF »
MNN6, a Member of the KRE2/MNT1 Family, Is the Gene for Mannosylphosphate Transfer in Saccharomyces cerevisiae.
X.-H. Wang, K.-i. Nakayama, Y.-i. Shimma, A. Tanaka, and Y. Jigami (1997)
J. Biol. Chem. 272, 18117-18124
   Abstract »    Full Text »    PDF »
Inhibition of Phagolysosomal Biogenesis by the Leishmania Lipophosphoglycan.
M. Desjardins and A. Descoteaux (1997)
J. Exp. Med. 185, 2061-2068
   Abstract »    Full Text »    PDF »
Functional Expression of the Murine Golgi CMP-Sialic Acid Transporter in Saccharomyces cerevisiae.
P. Berninsone, M. Eckhardt, R. Gerardy-Schahn, and C. B. Hirschberg (1997)
J. Biol. Chem. 272, 12616-12619
   Abstract »    Full Text »    PDF »
Golgi GDP-mannose Uptake Requires Leishmania LPG2. A MEMBER OF A EUKARYOTIC FAMILY OF PUTATIVE NUCLEOTIDE-SUGAR TRANSPORTERS.
D. Ma, D. G. Russell, S. M. Beverley, and S. J. Turco (1997)
J. Biol. Chem. 272, 3799-3805
   Abstract »    Full Text »    PDF »
The Yeast VRG4 Gene Is Required for Normal Golgi Functions and Defines a New Family of Related Genes.
J. B. Poster and N. Dean (1996)
J. Biol. Chem. 271, 3837-3845
   Abstract »    Full Text »    PDF »
Cloning of a Novel Inosine-Guanosine Transporter Gene from Leishmania donovani by Functional Rescue of a Transport-deficient Mutant.
N. S. Carter, M. E. Drew, M. Sanchez, G. Vasudevan, S. M. Landfear, and B. Ullman (2000)
J. Biol. Chem. 275, 20935-20941
   Abstract »    Full Text »    PDF »
Phosphoglycan Repeat-deficient Leishmania mexicana Parasites Remain Infectious to Macrophages and Mice.
T. Ilg, M. Demar, and D. Harbecke (2001)
J. Biol. Chem. 276, 4988-4997
   Abstract »    Full Text »    PDF »
Identification of a Conserved Motif in the Yeast Golgi GDP-mannose Transporter Required for Binding to Nucleotide Sugar.
X.-D. Gao, A. Nishikawa, and N. Dean (2001)
J. Biol. Chem. 276, 4424-4432
   Abstract »    Full Text »    PDF »
Substrate Recognition by UDP-galactose and CMP-sialic Acid Transporters. DIFFERENT SETS OF TRANSMEMBRANE HELICES ARE UTILIZED FOR THE SPECIFIC RECOGNITION OF UDP-GALACTOSE AND CMP-SIALIC ACID.
K. Aoki, N. Ishida, and M. Kawakita (2001)
J. Biol. Chem. 276, 21555-21561
   Abstract »    Full Text »    PDF »
Lipophosphoglycan is a virulence factor distinct from related glycoconjugates in the protozoan parasite Leishmania major.
G. F. Spath, L. Epstein, B. Leader, S. M. Singer, H. A. Avila, S. J. Turco, and S. M. Beverley (2000)
PNAS 97, 9258-9263
   Abstract »    Full Text »    PDF »



To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)