Physiological role of voltage-sensing phosphatase in mammals
| Project/Area Number |
16H02617
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
河合 喬文 大阪大学, 医学系研究科, 助教 (70614915)
筒井 秀和 北陸先端科学技術大学院大学, 先端科学技術研究科, 准教授 (30392038)
西澤 和久 帝京大学, 医療技術学部, 教授 (00260935)
大河内 善史 大阪大学, 医学系研究科, 助教 (90435818)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥44,070,000 (Direct Cost: ¥33,900,000、Indirect Cost: ¥10,170,000)
Fiscal Year 2018: ¥13,000,000 (Direct Cost: ¥10,000,000、Indirect Cost: ¥3,000,000)
Fiscal Year 2017: ¥13,130,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥3,030,000)
Fiscal Year 2016: ¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
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| Keywords | イオンチャネル / 精子 / 電位センサー / 膜電位 / イノシトールリン脂質 / 濃度勾配 / 運動性 / 脂質 / シグナル伝達 / タンパク質 / 酵素 / 蛋白質 |
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| Outline of Final Research Achievements |
Voltage-sensing phosphatase is a unique protein that transduces electrical signal in membrane into chemical signal. Despite its robust and deep understandings of molecular mechanisms, physiological function of VSP has remained unclear. In this study, we analyzed sperm of VSP deficient mouse by combining electrophysiology, fluorescence measurement, molecular dynamics simulation and mass spectrometry. VSP regulates potassium channel activity on sperm flagellum membrane via regulating the level and distribution of PI(4,5)P2. This is the first report on identification of physiological role of VSP in any animal species. It also gives the first case where the absolute level and distribution of phosphoinositide in sperm was shown to be critical for regulation of cellular function.
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| Academic Significance and Societal Importance of the Research Achievements |
これまで膜電位シグナルは、イオンチャネルの分布により規定されるということが教科書的な概念であったが、今回のVSPによるイノシトールリン脂質の分布によるイオンチャネルの制御の発見は、この固定概念を覆し、イオンチャネルの分布に加えて、脂質分子の分布が重要であることを初めて明らかにしたもので、その学術的な意義は大きい。VSPは動物種を超えて精子に発現しており、今回初めて明らかになった脂質分子の役割の理解を今後更に進めることで、不妊症の解決や創薬などを通して少子化社会の問題に資する可能性があるとともに、畜産などでの生殖技術や動物種多様性の保全などにむけた研究の基礎に資する可能性がある。
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Report
(4 results)
Research Products
(138 results)
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[Journal Article] Genetically encoded bioluminescent voltage indicator for multi-purpose use in wide range of bioimaging.2017
Author(s)
Inagaki S, Tsutsui H, Suzuki K, Agetsuma M, Arai Y, Jinno Y, Bai G, Daniels M, Okamura Y, Matsuda M, and Nagai T
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Journal Title
Scientific Reports
Volume: 7
Issue: 1
Pages: 42398-42398
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Function of voltage-sensing phosphatase in mouse sperm2019
Author(s)
Takahumi Kawai,Haruhiko Miyata, Hiroko Nakanishi,Souhei Sakata,Yoshifumi Okochi,Masahiko Watanabe,Toyoshi Fujimoto,Kenji Sakimura, Takehiko Sasaki,Masahito Ikawa,Yasushi Okamura
Organizer
60th International Conference on the Bioscience of Lipids（ICBL2019）
Related Report
Int'l Joint Research
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[Presentation] A new mechanism of Ca2+-independent voltage-dependent secretion in dorsal root ganglion neurons2019
Author(s)
Zhuan Zhou, Yuan Wang, Hiroki Arima, Rong Huang, Yuqi Hang, Xingyu Du, Feipeng Zhu, Zuying Chai, Changhe Wang, Yasushi Okamura
Organizer
The 9th Federation of the Asian and Oceanian Physiological Societies Congress (FAOPS2019) , 第96回日本生理学会年会 合同大会
Related Report
Int'l Joint Research
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[Presentation] Functional analysis of voltage-sensing phosphatase in mouse sperm2019
Author(s)
Takafumi Kawai, Haruhiko Miyata, Hiroki Nakanishi, Souhei Sakata, Yoshifumi Okochi, Masahiko Watanabe, Kenji Sakimura, Takehiko Sasaki, Masahito Ikawa, Yasushi Okamura
Organizer
The 9th Federation of the Asian and Oceanian Physiological Societies Congress (FAOPS2019) , 第96回日本生理学会年会 合同大会
Related Report
Int'l Joint Research
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[Presentation] Development of a chemiluminescent voltage indicator applicable to brain activity recording in freely moving multiple mice2017
Author(s)
Shigenori Inagaki, Masakazu Agetsuma, Hidekazu Tsutsui, Shinya Ohara, Yoshiyuki Arai, Kazushi Suzuki, Yuka Jinno, Tomoki Matsuda, Toshio Iijima, Yasushi Okamura, Takeharu Nagai
Organizer
第40回日本神経科学大会
Related Report
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[Presentation] Molecular dynamics study of kinetics of the voltage-gated proton channel VSOP/Hv1 under electric fields2017
Author(s)
Hiroko X. Kondo, Yasushige Yonezawa, Naoyuki Miyashita, Masayo Iwaki, Kohei Takeshita, Yuichiro Fujiwara, Matsuyuki Shirota, Kengo Kinoshita, Yasushi Okamura, Atsushi Nakagawa, Hideki Kandori, Yu Takano
Organizer
第55回日本生物物理学会年会
Related Report
Invited
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[Presentation] Molecular dynamics study of kinetics of the voltage-gated proton channel VSOP/Hv1 under electric fields2017
Author(s)
Hiroko X. Kondo, Yasushige Yonezawa, Naoyuki Miyashita, Masayo Iwaki,Kohei Takeshita, Yuichiro Fujiwara, Matsuyuki Shirota, Kengo Kinoshita, Yasushi Okamura, Atsushi Nakagawa, Hideki Kandori, Yu Takano
Organizer
第54回日本生物物理学会年会
Related Report
Invited
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[Book] 脂質クオリティ2018
Author(s)
岡村康司、水谷夏希、大河内善史
Total Pages
220
Publisher
羊土社
ISBN
9784758103718
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[Book] ガイトン生理学 原著第13版2018
Author(s)
石川義弘、岡村康司（総監訳）、尾仲達史、河野憲二
Total Pages
1100
Publisher
エルゼビア・ジャパン株式会社
ISBN
9784860347741
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