Mechanism of the cytotoxic effect exerted by type C botulinum hemagglutinin
| Project/Area Number |
25860319
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Bacteriology (including mycology)
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| Research Institution | Osaka University |
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Principal Investigator |
SUGAWARA Yo 大阪大学, 微生物病研究所, 特任助教(常勤) (70452464)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | ボツリヌス毒素 / ヘマグルチニン / シアル酸 / ガングリオシド / GM3 / 糖鎖アレイ / アクチン骨格 / GM3合成酵素 / 細胞接着 / アクチン細胞骨格 / 糖鎖 |
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| Outline of Final Research Achievements |
Botulinum neurotoxin is conventionally divided into seven serotypes designated A-G, and is produced as large protein complexes through associations with nontoxic components, such as hemagglutinin (HA). Type C HA (HA/C) is known to affect cell morphology and viability, the mechanism of which remains unknown. In this study, I identified GM3 as the target molecule of HA/C. I found that sialic acid binding of HA is essential for the activity. It was abolished when cells were pretreated with an inhibitor of ganglioside synthesis. Consistent with this, HA/C bound to GM3 and a-series gangliosides in a glycan array. In parallel, I isolated clones resistant to HA/C activity from a susceptible mouse fibroblast strain. These cells lacked the expression of ST-I, the enzyme that transfers sialic acid to lactosylceramide to yield GM3. In addition, these clones became sensitive to HA/C activity when GM3 was expressed by transfecting the ST-I gene. Thus, HA/C affects cells in a GM3-dependent manner.
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Report
(4 results)
Research Products
(3 results)
