Novel regulatory mechanism of semaphorin in endosomal trafficking
| Project/Area Number |
23390069
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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 |
General medical chemistry
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| Research Institution | Osaka University |
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Principal Investigator |
TOYOFUKU Toshihiko 大阪大学, 免疫学フロンティア研究センター, 准教授 (60322179)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000)
Fiscal Year 2013: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2012: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2011: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
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| Keywords | セマフォリン / 網膜色素変性症 / 網膜色素上皮 / 色素上皮細胞 / 視細胞 / semaphorin 4A / 網膜色素上皮細胞 / Sema4A / 細胞内膜輸送制御 |
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| Research Abstract |
Sema4A was identified in a family suffering from retinitis pigmentosa (RP). We generated the Sema4A-deficient mice and found the degeneration of photoreceptors. This result supported the hypothesis that Sema4A is the one of the causative genes for the human retinitis pigmentosa. Retinal pigment epithelial cells (RPE), where Sema4A is expressed, prevent photoreceptors from light-induced apoptosis and support the retinoid recycling which regenerates the photo-converted retinoid to normal one. Sema4A was found to activate these processes through regulating the endosomal trafficking. We further generated the mice carrying the mutated Sema4A, which were identified in human RP and found that these mutations in Sema4A are responsible for the RP. The injection of retrovirus carrying wild-type Sema4A successfully rescued the defects in photoreceptors in mutated mice. This result provided the possibility that the RP can be improved by the gene-transfer of Sema4A into RPE.
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Report
(4 results)
Research Products
(11 results)
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[Journal Article] A point mutation in Semaphorin 4A associates with defective Endosomal sorting and causes retinal degenerative diseases2013
Author(s)
Nojima S, Toyofuku T, Kamao H, Ishigami C, Kaneko J, Okuno T, Takamatsu H, Ito D, Kang S, Kimura T, Yoshida Y, Morimoto K, Maeda Y, Ogata A, Ikawa M, Morii E, Aozasa K, Takagi J, Takahashi M, Kumanogoh A
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Journal Title
Nat Commun
Volume: 4
Pages: 1406-1406
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