Functional research of a novel protein comprising ciliated membrane
| Project/Area Number |
17K15119
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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 |
Cell biology
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| Research Institution | Nara Institute of Science and Technology |
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Principal Investigator |
NISHI Akiko 奈良先端科学技術大学院大学, 先端科学技術研究科, 助教 (50772422)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 細胞膜突起 / Rhoシグナル経路 / 塩化物イオン / 繊毛 / 眼科疾患 / 一次繊毛 / 膜タンパク質 / 繊毛病 / 変異マウス / シグナル伝達 |
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| Outline of Final Research Achievements |
The membrane protein Prominin-1 (Prom1) is known to localize to the protrusions. Mutation(s) in Prom1 gene is causative for retinitis pigmentosa, which is a hereditary retinal disease, however, the underlying mechanism(s) have been elusive. Based on the previous finding that the over-expression of Prom1 induced cell membrane protorusions, in this study, I sought to elucidate the mechanism of cell membrane protrusion formation mediated by Prom1. Firstly, Prom1-induced protrusions were formed in a manner dependent cholesterol. Secondary, with detailed domain mapping of Prom1, five amino acids that is essential for protrusion formation were identified in the carbonyl cytosolic region. Moreover, it was revealed that the small GTPase Rho and its downstream kinase ROCK are essential for Prom1-induced protrusion formation. Eventually, Prom1 was required for the chloride ion efflux induced by calcium ion uptake, which is closely associated with protrusion formation.
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| Academic Significance and Societal Importance of the Research Achievements |
Prom1遺伝子異常が遺伝性眼科疾患である網膜色素変性症やスターガルト病を誘発することが報告された。このことにより、Prom1タンパク質の重要性は発生過程の幹細胞だけではなく、視細胞における恒常性機能維持の局面でも必須の役割を果たすことが示唆されている。しかし、Prom1タンパク質の機能解析は進んでおらず、Prom1が眼科疾患を引き起こす直接の原因や、Prom1が惹起する細胞内シグナル経路については不明な点が多い。本研究において、Prom1における突起形成機構と塩化物イオンの流出活性という新たな機能を提唱したことにより、治療に向けた基礎が構築された。
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Report
(3 results)
Research Products
(13 results)
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[Journal Article] Membrane Protrusion Formation Mediated by Rho/ROCK Signalling and Modulation of Chloride Flux2018
Author(s)
Akiko Hori, Kenji Nishide, Yuki Yasukuni, Kei Haga, Wataru Kakuta, Yasuyuki Ishikawa, Matthew J Hayes, Shin-ichi Ohnuma, Hiroshi Kiyonari, Kazuhiro Kimura, Toru Kondo, Noriaki Sasai
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Journal Title
Related Report
Peer Reviewed / Open Access
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