ANALYSIS OF PHYSIOLOGICAL FUNCTION OF LIPID SIGNALLING SYSTEM
| Project/Area Number |
18370053
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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 |
Functional biochemistry
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| Research Institution | University of Tsukuba |
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Principal Investigator |
KANAHO Yasunori University of Tsukuba, GRADUATE SCHOOL OF COMPREHENSIVE HUMAN SCIENCES, PROFESSOR (00214437)
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| Co-Investigator(Kenkyū-buntansha) |
横関 健昭 筑波大学, 大学院人間総合科学研究科, 講師 (80373405)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥17,170,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥1,770,000)
Fiscal Year 2007: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Fiscal Year 2006: ¥9,500,000 (Direct Cost: ¥9,500,000)
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| Keywords | single transduction / lipid kinase / synaptic vesicle / ARF6 / knockout mice / endocytosis / AP-2 complex / PIP5K / 低分子量G蛋白質 / アレルギー / 神経 / PIP5Kγ661 / シナプス小胞 |
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| Research Abstract |
The lipid kinase phosphatidylinositol 4-phosphate 5-kinase (PIP5K) phosphorylates phosphatidylinositol 4-phosphate to produce phosphatidylinositol 4,5-bisphosphate (PIP2), which functions as a lipid signaling molecule. Three isozymes for mammalian PIP5K, α β and γ, and three splicing variants of γ type of PIP5K, γ635, γ661 and γ687, have been identified. We have been investigating activation mechanisms and physiological functions of each PIP5K isozyme to understand the molecular multiplicity of PIP5K. During 2 years of this project, we obtained the results described below.
1. Specific partner protein of PIP5K γ661
PIP5K γ661 of PIP5K isozymes and splicing variants, was found to specifically interact with and is activated by the adaptor complex AP-2 in mouse hippocampal neurons. Furthermore, it was found that the interaction of these molecules is absolutely required for the clathrin-dependent synaptic vesicle endocytosis induced by depolarization, in mouse hippocampal neurons.
2. Specific partner protein of PIP5Kβ
PIP5Kβ of PIP5K isozymes specifically interact with KIF2A. The interaction stimulated PIP5Kβ kinase activity and microtubule depolymerizing activity of KIF2A. Finally, the interaction of these two molecules was found to negatively regulate axonal outgrowth of mouse hippocampal neurons.
3. PIP5K binding site for its activator ARF6
The small G protein ARF6 activates PIP5K. We identified that ARF6 binds to the kinase core domain of PIP5K, which is highly conserved among PIP5K isozymes.
4. Preparation and analysis of PIP5K α knockout mice
We prepared PIP5K α knockout mice, which have not yet been reported. These mice were apparently healthy and any defects were not observe.
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Report
(3 results)
Research Products
(58 results)
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[Journal Article] Control of cell polarity and motility by the Ptdlns(3,4,5)P(3) phosphatase SHIP12007
Author(s)
Nishio M, Watanabe K, Sasaki J, Taya C, Takasuga S, lizuka R, Balla T, Yamazaki M, Itoh R, Kuroda S, Horie Y, Forster I, Mak T. S, Yonekawa H, Penninger J. M, Kanaho Y, Suzuki A, Sasaki T
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Journal Title
Nat. Cell Biol 9(peer review)
Pages: 36-44
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Crucial role of the small GTPase ARF6 in hepatic cord formation during liver developent2006
Author(s)
Suzu T, Kanai Y, Hara T, Sasaki T, Khara M, Maehama T, Taya C, Shitara H, Yonekawa H, Frohaman M. A., Yokozeki T. and Kanaho Y
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Journal Title
Mol. Cell. Biol 26(peer review)
Pages: 6149-6156
Description
「研究成果報告書概要(欧文)」より
Related Report
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