| Project/Area Number |
07309013
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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 | 総合 |
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| Research Field |
広領域
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| Research Institution | Graduate School of Science, Osaka University |
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Principal Investigator |
KAWAMURA Satoru Graduate School of Science, Osaka University, Professor, 大学院・理学研究科, 教授 (80138122)
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| Co-Investigator(Kenkyū-buntansha) |
HIDAKA Hiroyoshi Medical School, Nagoya University, Professor, 医学部, 教授 (80100171)
MIKI Naomasa Medical School, Osaka University, Professor, 大学院・医学部, 教授 (40094445)
TOKUNAGA Fumio Graduate School of Science, Osaka University, professor, 大学院・理学研究科, 教授 (80025452)
TAKAMATSU Ken Medical School, Toho University, Professor, 医学部, 教授 (90154898)
KUNO Takayoshi Medical School, Kobe University, Professor, 医学部, 教授 (50144564)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 1996: ¥7,800,000 (Direct Cost: ¥7,800,000)
Fiscal Year 1995: ¥7,000,000 (Direct Cost: ¥7,000,000)
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| Keywords | calcium-binding proteins / Neuron / S-modulin / Hippocalcin / recoverin / neurocalcin / NVP / NVP / S-モジュリン / カルモジュリン / リン酸化 / 神経 |
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| Research Abstract |
(1) Molecular cloning of new family members of neuron-specific calcium-binding proteins (NCaP) were performed : we obtained clones of frog rod photoreceptor S-modulin ; frog cone photoreceptor s26 ; rat hippocampal HLP3 and HLP4.
(2) Expression systems in E.Coli are now available in some of the NCaPs. They included Hippocalcim, S-modulin and s26.
(3) Hippocalcin genome gene was isolated and it was found that this gene is located on the 2nd human chromosome. The transcription mechansism of rat hippocalcin gene was investigated and the sites of enhancer and silencer were identified.
(3) The target proteins of S-modulin and neurocalcin were found. In the case of S-modulin, rhodopsin kinase was found to be the target protein. This was done by functional analysis and also structural analysis using a liker conjugated with S-modulin. The possible target of neurocalcin was found to be S100b and/or tublin b.
(4) The N-terminus of recoverin is acylated with myristic acid. The role of this lipid modification was examined. It was found that myristoylation facilitates the binding of recoverin to rhodopsin kinase. It was also demonstrated that the lipid modification induces facilitation of the targetting of rhodopsin kinase to disk membranes. The membrane binding is weaker in s26 than S-modulin. It was found that part of this difference is due to a lack of positive charges in s26 at amino acid residues close to C-terminus.
(5) Possible role of calmodulin on the phosphorylation of muscarinic acetylcholine receptor was investigated. The calcium-bound form of calmodulin inhibited the receptor phosphorylation by GRK2.
(6) The role of each domain of calmodulin was investigated using chimera calmodulin. To exert calmodulin function, co-ordinated calcium binding to a pair of calcium-binding site were required.
(7) Possible role of calcineulin were examined. It was found that calcineulin may inhibit long term potentiation, a possible machinery of memory.
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