2007 Fiscal Year Final Research Report Summary
Functional analysis of BDNF protein using Proteomics techinology
| Project/Area Number |
18500259
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neuroscience in general
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| Research Institution | National Institute of Advanced Industrial Science and Technology |
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Principal Investigator |
KOJIMA Masami National Institute of Advanced Industrial Science and Technology, Research Institute for Cell Engineering (RICE), National Institute of Advanced Science and Technology(AIST), Research Group leader (40344171)
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| Co-Investigator(Kenkyū-buntansha) |
UEGAKI Koichi Research Institute for Cell Engineering (RICE), National Institute of Advanced Science and Technology (AIST), Senior Research Scientist (00356544)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Neuron / Protein / DNA / Brain / 神経科学 / 脂質 |
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| Research Abstract |
ProBDNF, through activation of p75NTR, exerts functions opposite to those of mature BDNF (mBDNF). Thus, proteolytic conversion of proBDNF to mBDNF determines the direction of BDNF actions. Here we characterize two rare human SNPs (R125M and R127L) that substitute two arginines adjacent to the cleavage site. The SNPs markedly inhibited the endo-proteolytic cleavage of proBDNF. The resulting cleavage-resistant proBDNF facilitated apoptosis of cerebellar granule neurons (CGNs) and suppressed neurite outgrowth of cultured basal forebrain cholinergic neurons (BFCNs). Knock-in mice (BDNF pro/pro) with the arginine substitutions exhibited a smaller cerebellum, enhanced CGN apoptosis and decreased proliferation of CGN precursors. In basal forebrain, inhibition of proBDNF cleavage did not affect BFCNs survival but suppressed cholinergic afferents to the hippocampus. These effects were caused by an increase in proBDNF rather than the decrease in mBDNF, since crossing BDNF pro/pro with p75NTR mutant mice rescued the cellular phenotypes. These results reveal the in vivo function of proBDNF and underscore the importance of proBDNF cleavage.
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[Journal Article] Regulation of dendritogenesis via a lipid raft-associated Ca2+/calmodulin-dependent protein kinase CLICK-III/CaMKI gamma2007
Author(s)
Takemoto-Kimura S, Ishihara-Ageta N, Nonaka M, Adachi-Morishima A, Mano T, Okamura M, Fujii H, Fuse T, Hoshino M, Suzuki S, Kojima M, M.Mishina M, Okuno H, Bito H
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Journal Title
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Regulation of dendritogenesis via a lipid raft-associated Ca2+/calmodulin-dependent protein kinase CLICK-III/CaMKI gamma2007
Author(s)
Takemoto-Kimura S, Ishihara-Ageta N, Nonaka M, Adachi-Morishima A, Mano T, Okamura M, Fujii H, Fuse T, Hoshino M, Suzuki S, Kojima M, M. Mishma M, Okuno H, Bito H
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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