| Project/Area Number |
18K15019
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 48020:Physiology-related
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| Research Institution | National Institute for Physiological Sciences |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | two-pore channel / TPC / 電位依存性Na+チャネル / イオンチャネル / 電気生理学 / 受精 / Na+チャネル / Two-pore Na+ channel / 膜電位依存性イオンチャネル / 膜タンパク質 |
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| Outline of Final Research Achievements |
Two-pore channel 3 (TPC3) is a voltage-gated Na+ channel thought to be expressed in oocytes. We analyzed TPC3 for the involvement in fertilization and polyspermy, using Xenopus oocytes as an expression system and two-electrode voltage clamp technique. The functional analyses with pharmacological treatment and exogenous mutant protein expression suggested that TPC3 is regulated by the factors involved in polyspermy. We also found that the Na+ current endogenous in Xenopus oocytes, which shows a TPC3-like activation mode, is phosphoinositide-sensitive, as well as TPC3. Furthermore, we analyzed the molecular basis of the phosphoinositide sensitivity of TPC3 and proposed a hypothesis that explains it at the atomic level.
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| Academic Significance and Societal Importance of the Research Achievements |
TPC3はヒトデ卵母細胞などでの発現と生理的役割が示唆されていたが、その詳細、特に制御分子に関する知見はほとんど得られていなかった。本研究では、TPC3が生理的に実際に機能する場である卵母細胞を用い、多精拒否に関わる分子などの関与を示す結果を得ることができた。また、PI感受性についての詳細な解析の結果は、TPC3も含めてすべてのサブタイプがPI感受性を持つというTPCファミリーの理解に重要な知見を提供するとともに、一般的なPI認識メカニズムの理解を深めることに寄与すると期待される。
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