2002 Fiscal Year Final Research Report Summary
Function of neuron-specific X11L protein (human LIN10) and its concerning in neuraldegeneration
| Project/Area Number |
12470494
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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 | HOKKAIDO UNIVERSITY (2001-2002)
The University of Tokyo (2000) |
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Principal Investigator |
TOSHIHARU Suzuki HOKKAIDO UNIV. GRADUATE SCH. OF PHARMACEUTICAL SCI., 大学院・薬学研究科, 教授 (80179233)
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| Co-Investigator(Kenkyū-buntansha) |
TATSUNORI Seki Juntendo Univ. Sch. Of Medicine, 医学部, 講師 (20175417)
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| Project Period (FY) |
2000 – 2002
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| Keywords | ALZHEIMER'S DISEASE / β-AMYLOID / APP / NF-kB / X11-like / XB51 / ノックアウトマウス |
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| Research Abstract |
In Alzheimer's disease (AD), the β-amyloid peptide (Aβ) is thought to be produced as a results of the aberrant metabolism of APP. Various types of proteins associate with these motifs of APP cytoplasmic domain and modulate metabolism, trafficking and function of APP. We isolated novel APP binding protein, X11L. Phosphotyrosine interaction domain of X11L binds to NPTY motif of APP. This interaction stabilized the APP metabolism and results in the suppression of β-amyloid production. To analyze regulatory mechanism of X11L on APP metabolism, we isolated X11L binding proteins using Yeast two-hybrid system. We found NF-_kB, XB51, and novel membrane protein associated with X11L. Interaction of X11L with these proteins regulated association of APP with X11L resulting regulateion of APP metabolism.
APP is phosphorylated at Thr668 in the cytoplasmic domain. This phosphorylation suppresses the associateion of some type such as Fe65 of APP binder to NPTY motif. X11L did not affect its interaction to APP by the phosphorylation. The binding of X11L to the cytoplasmic domain of APP stabilized the phosphorylation level of APP. These observations suggest that association of X11L with APP can modify the metabolism and function of APP.
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[Publications] Sai X., Kawamura Y., Kokame K., Yamaguchi H., Shiraishi H., Suzuki R., Suzuki T., Kawaichi M., Miyata T., Kitamura T., De Strooper B., Yanagisawa K., Komano H.: "Endoplasmic reticulum stress-inducible protein, Herp, enhances presenilin-mediated generation of amyloid β-protein"J. Biol. Chem.. 277. 12915-12920 (2002)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Hase M., Yagi Y., Taru H., Tomita S., Sumioka A., Hori K., Miyamoto K., Sasamura T., Nakamura M, Matsuno K., Suzuki T.: "Expression and characterization of the Drosophila X11-like/Mint protein during neural development"J. Neurochem.. 81. 1223-1232 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Ishii J., Adachi H., Aoki J., Koizumi H., Tomita S., Suzuki T., Tsujimoto M., Inoue K., Arai H.: "SREC-II, a new member of the scavenger receptor type F family, tans-interacts with SREC-I through its extracellular domain."J. Biol. Chem.. 277. 39696-39702 (2002)
Description
「研究成果報告書概要(欧文)」より
