1996 Fiscal Year Final Research Report Summary
Regulation of intracellular APP metabolism by phosphorylation
| Project/Area Number |
07457536
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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 |
Biological pharmacy
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SUZUKI Toshiharu The University of Tokyo, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (80179233)
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| Project Period (FY) |
1995 – 1996
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| Keywords | Alzheimer's Disease / amyloid precursor protein / beta-amyloid / protein phosphorylation / transcytosis / neuron |
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| Research Abstract |
beta-amyloid precursor protein (APP) containes three known phosphorylation sites in its cytoplasmic domain. We report here that phosphorylation of APP at Thr668, one of the three sites, is a neuron-specific phenomenon. In adult rat neuronal tissues and in primary cultures of rat hippocampal neuron, the phosphorylated form of APP (PiAPP) is localized in somatic plasma membrane and on neurites although APP distributes in somata and on neurites. Inhibition of axonal tranport results in complete disaappearance of PiAPP in primary cultures of rat hippocampal neuron, and disruption of transcytosis with brefeldin A altered the distribution of PiAPP in the neuron. Our findings indicate that APP is phosphorylated at the nerve terminal after fast axonal transport, and PiAPP is redistributed into plasma membrane and dendrites by transcytosis. Because the production of beta-amyloid (Abeta) is physiologically restricted to neuronal cells and because the phosphorylation of APP also is a neuronally specific event, analysis of the mechanism of APP phosphorylation may contribute to understanding the molecular mechanism of Ab production in Alzheimer's disease (AD).
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[Publications] Toshiharu Suzuki, Kanae Ando, Toshio Isohara, Masaki Oishi, Gloria S.Lim, Yasushi Satoh, Wilma Wasco, Rudolph E.Tanzi, Angus C.Nairn, Paul Greengard, Samuel E.Gandy and Yutaka Kirino: "Phosphorylation of Alzheimer's beta-amyloid precursor-like proteins" Biochemistry. (in press). (1997)
Description
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