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一条影响利什曼原虫毒力糖缀合物的特殊途径。

A specialized pathway affecting virulence glycoconjugates of Leishmania.

作者信息

Descoteaux A, Luo Y, Turco S J, Beverley S M

机构信息

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

出版信息

Science. 1995 Sep 29;269(5232):1869-72. doi: 10.1126/science.7569927.

DOI:10.1126/science.7569927
PMID:7569927
Abstract

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.

摘要

对于致病性和传播而言,原生动物寄生虫利什曼原虫必须在细胞表面组装一种复杂的糖脂,即脂磷壁酸聚糖(LPG)。功能互补鉴定出了LPG2基因,该基因编码一种高尔基体内膜蛋白,与LPG生物合成的细胞内区室化有关。Ipg2突变体仅缺少特征性的二糖磷酸重复序列,这些重复序列通常存在于LPG以及其他被认为对感染性至关重要的表面或分泌分子上。相比之下,一个相关的酵母基因VAN2/VRG4对高尔基复合体的正常功能至关重要且是必需的。这些结果表明,LPG2参与了一条特殊的致病途径,这可能为化疗提供一个有吸引力的靶点。

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A specialized pathway affecting virulence glycoconjugates of Leishmania.一条影响利什曼原虫毒力糖缀合物的特殊途径。
Science. 1995 Sep 29;269(5232):1869-72. doi: 10.1126/science.7569927.
2
Leishmania LPG3 encodes a GRP94 homolog required for phosphoglycan synthesis implicated in parasite virulence but not viability.利什曼原虫LPG3编码一种GRP94同源物,该同源物是磷酸聚糖合成所必需的,与寄生虫毒力有关,但与生存能力无关。
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Identification of genes mediating lipophosphoglycan biosynthesis by functional complementation of Leishmania donovani mutants.通过杜氏利什曼原虫突变体的功能互补鉴定介导脂磷酸聚糖生物合成的基因。
Ann Trop Med Parasitol. 1995 Dec;89 Suppl 1:11-17. doi: 10.1080/00034983.1995.11813009.
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Leishmania donovani lacking the Golgi GDP-Man transporter LPG2 exhibit attenuated virulence in mammalian hosts.缺乏高尔基体GDP-甘露糖转运蛋白LPG2的杜氏利什曼原虫在哺乳动物宿主中的毒力减弱。
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Reduced expression of lipophosphoglycan (LPG) and kinetoplastid membrane protein (KMP)-11 in Leishmania donovani promastigotes in axenic culture.体外培养的杜氏利什曼原虫前鞭毛体中脂磷壁酸聚糖(LPG)和动基体膜蛋白(KMP)-11的表达降低。
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Golgi GDP-mannose uptake requires Leishmania LPG2. A member of a eukaryotic family of putative nucleotide-sugar transporters.高尔基体GDP-甘露糖摄取需要利什曼原虫LPG2。LPG2是假定的核苷酸糖转运体真核家族的一员。
J Biol Chem. 1997 Feb 7;272(6):3799-805.
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Identification of a compensatory mutant (lpg2-REV) of Leishmania major able to survive as amastigotes within macrophages without LPG2-dependent glycoconjugates and its significance to virulence and immunization strategies.鉴定一种杜氏利什曼原虫的补偿性突变体(lpg2-REV),该突变体能够在巨噬细胞内作为无鞭毛体存活,且不依赖LPG2依赖性糖缀合物,及其对毒力和免疫策略的意义。
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The Leishmania GDP-mannose transporter is an autonomous, multi-specific, hexameric complex of LPG2 subunits.利什曼原虫GDP-甘露糖转运蛋白是一种由LPG2亚基组成的自主、多特异性六聚体复合物。
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An in vitro system for developmental and genetic studies of Leishmania donovani phosphoglycans.用于杜氏利什曼原虫磷酸化聚糖发育和遗传研究的体外系统。
Mol Biochem Parasitol. 2003 Aug 11;130(1):31-42. doi: 10.1016/s0166-6851(03)00142-7.
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Lipophosphoglycan is a virulence factor distinct from related glycoconjugates in the protozoan parasite Leishmania major.脂磷壁酸聚糖是一种与原生动物寄生虫硕大利什曼原虫中的相关糖缀合物不同的毒力因子。
Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):9258-63. doi: 10.1073/pnas.160257897.

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