Biosynthesis and functions of GPI-anchored proteins in African trypanosomes
| Project/Area Number |
17390121
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Parasitology (including Sanitary zoology)
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| Research Institution | OSAKA UNIVERSITY |
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Principal Investigator |
KINOSHITA Taroh Osaka University, Research Institute for Microbial Diseases, Professor, 微生物病研究所, 教授 (10153165)
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| Co-Investigator(Kenkyū-buntansha) |
MORITA Yasuhiro Osaka University, Research Institute for Microbial Diseases, Specially Appointed Research Associate, 微生物病研究所, 特任助手 (70397769)
ASIDA Hisashi Kyoto University, Graduate School of Biostudies, Research Associate, 大学院・生命科学研究科, 助手 (40379087)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2006: ¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 2005: ¥7,400,000 (Direct Cost: ¥7,400,000)
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| Keywords | glycosylphosphatidylinositol / sleeping sickness / Trypanosoma brucei / protozoa / sialic acid / 睡眠病トリパノソーマ / 脂肪酸 |
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| Research Abstract |
A protozoan parasite Trypanosoma brucei is coated by glycosylphosphatidylinositol (GPI) anchored proteins. During GPI biosynthesis, inositol in phosphatidylinositol becomes acylated. Inositol is deacylated prior to attachment to variant surface glycoproteins (VSG) in the bloodstream form whereas it remains acylated in procyclins in the procyclic form. We have cloned a T brucei GPl inositol deacylase (GPIdeAc2). In accordance with the acylation / deacylation profile, GPIdeAc2 was expressed at a 6-fold higher level in the bloodstream form than the procyclic form. Knockdown of GPIdeAc2 in the bloodstream form caused accumulation of an inositol-acylated GPI, a decreased VSG expression on the cell surface and slower growth, indicating the essential role of inositol-deacylation for growth of the bloodstream form. Overexpression of GPIdeAc2 in the procyclic form caused an accumulation of GPI lacking inositol-linked acyl chain and decreased cell surface procyclins due to release into the cultu
… More
re medium, indicating that overexpression of GPIdeAc2 is deleterious to the surface coat of the procyclic form.
In the fly's intestine, the trypanosomes survive digestive and trypanocidal environments, proliferate and translocate into the salivary gland where they become infectious to the next mammalian host. For the successful survival in tsetse flies, the trypanosomes use trans-sialidase to transfer sialic acids, which they cannot synthesize, from host's glycoconjugates to the GPIs that are abundantly expressed on their surface. T.brucei has at least 8 trans-sialidase like genes and the enzyme activity has been shown in only one of them, TSB38p. We cloned other genes and found that two of them, termed TS550band TS290b, do not have the enzyme activity. One of them, termed TS270b, clearly had trans-sialidase activity. Co-transfection of soluble forms of TSB38p and TS270b into TbGPI8 knockout trypanosomes resulted in attachment of additive amounts of sialic acid onto the parasites, suggesting that the two isoforms had different substrate specificities. Less
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Report
(3 results)
Research Products
(8 results)
