STUDIES ON FUNCTION AND SHIGNALING MECHANISM OF LIPID SIGNALING MOLECULE-PRODUCING ENZYME FOR ESTABLISHMENT OF HIGHLY ORGANIZED BRAIN FUNCTION
Project/Area Number |
16370091
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Cell biology
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Research Institution | UNIVERSITY OF TSUKUBA (2005) Tokyo Metropolitan Organization for Medical Research (2004) |
Principal Investigator |
KANAHO Yasunori UNIVERSITY OF TSUKUBA, GRADUATE SCHOOL OF COMPREHENSIVE HUMAN SCIENCES, PROFESSOR, 大学院・人間総合科学研究科, 教授 (00214437)
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Co-Investigator(Kenkyū-buntansha) |
MAEHAMA Tomohiko TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH, TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE, INVESTIGATOR, 東京都臨床医学総合研究所, 研究員 (40322755)
YOKOZEKI Takeaki UNIVERSITY OF TSUKUBA, GRADUATE SCHOOL OF COMPREHENSIVE HUMAN SCIENCES, ASSOCIATE PROFESSOR, 大学院・人間総合科学研究科, 講師 (80373405)
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Project Period (FY) |
2004 – 2005
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Project Status |
Completed (Fiscal Year 2005)
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Budget Amount *help |
¥15,500,000 (Direct Cost: ¥15,500,000)
Fiscal Year 2005: ¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 2004: ¥8,100,000 (Direct Cost: ¥8,100,000)
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Keywords | Signaling lipid-producing enzyme / PIP5Kβ / Spine / PIP5Kγ661 / AP-2 adaptor complex / Synaptic vesicle / Endocytosis / Signal transduction / 脂質性シグナル分子産生酵素 / 脂質シグナル分子 / ホスホリパーゼD / PIP5K / 肥満細胞 / ヒスタミン放出反応 / ノックアウトマウス / 高次脳機能 / アナフィラキシー |
Research Abstract |
We have investigated activation mechanisms and physiological functions of phosphatidylinositol 4-phosphate 5-kinase (PIP5K) which produces the pleiotropic phospholipid, phosphatidylinositol 4,5-bisphosphate, in neuronal cells. So far, we have obtained the results shown below. 1.Regulation of dendritic spine by PIP5Kβ. In mouse, PIP5Kβ was found that its expression pattern was almost the same as that of the spine marker protein PSD95 during development, and it was fractionated in the same fraction of PSD95,suggesting that PIP5Kβ functions in spines. Furthermore, we found that overexpression of wild type of PIP5Kβ in primary culture of mouse hippocampal neurons decreased the number of spines. In contrast, overexpression of a kinase-deficient mutant of PIP5Kβ increased spines. These results suggest that PIP5Kβ negatively regulates spine formation. 2. Novel interaction of PIP5Kγ661 with AP-2 adaptor complex plays a crucial role in synaptic vesicle endocytosis in hippocampal neurons. We found that PIP5Kγ661, of three PIP5K isozymes, α, β, and γ, and two splicing variants of PIP5Kγ, γ635 and γ661, specifically interacts with AP-2 complex. PIP5Kγ661 bound to the Ear domain of AP-2 through its C-terminal 26 amino acid tail. Furthermore, it was found that the interaction between PIP5Kγ661 and AP-2 is essential for depolarizing-dependent synaptic vesicle endocytosis.
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Report
(3 results)
Research Products
(26 results)
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[Journal Article] Regulation of anaphylactic responses by phosphatidylinositol phosphate kinase type I α.2005
Author(s)
J.Sasaki, T.Sasaki, M.Yamazaki, K.Matsuoka, C.Taya, H.Shitara, S.Takasuga, M.Nishio, K.Mizuno, T.Wada, H.Miyazaki, H.Watanabe, R.Iizuka, S.Kubo, S.Murata, T.Chiba, T.Maehama, MA.Frohman, K.Tanaka, JM.Penninger, H.Yonekawa, A.Suzuki, Y.Kanaho
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Journal Title
J.Exp.Med. 201
Pages: 859-870
Description
「研究成果報告書概要(欧文)」より
Related Report
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