Characterization of the enzymatic properties of γ-secretase

γ-分泌酶酶学特性的表征

• 批准号: 17025008
• 负责人: IHARA Yasuo
• 金额: $ 102.85万
• 依托单位: Doshisha University (2007-2009)The University of Tokyo (2005-2006)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17025008/
• 关键词: Alzheimer disease; γセクレターゼ; γ切断; ε切断; トリペプチド仮説; アミロイドβタンパク; Aβ産生; 膜内分解; アルツハイマー病; APP; 1型膜タンパク質; αヘリックス; 脳神経疾患; 脳・神経; 認知症; タンパク質; 酵素; アミロイドβタンパク質

How the cleavage proceeds within the membrane has long been enigmatic. We previously hypothesized that βCTF is cleaved first at the membrane-cytoplasm boundary, producing two long Ass, Aβ48 and Aβ49, which are processed further by releasing three residues at each step to produce Aβ42 and Aβ40, respectively. To test this hypothesis, we used LC-MS/MS to quantify the specific tripeptides that are postulated to be released. Using CHAPSO-reconstituted γ-secretase system, we confirmed that Aβ49 is converted to Aβ43/40 by successively releasing two or three tripeptides, and that Aβ48 is converted to Aβ42/38 by successively releasing two tripeptides or these plus an additional tetrapeptide.

细胞膜内的分裂是如何进行的一直是个谜。我们之前假设βCTF首先在膜-细胞质边界裂解，产生两个长的A β，Aβ48和Aβ49，它们通过在每个步骤释放三个残基而进一步加工，分别产生Aβ42和Aβ40。为了验证这一假设，我们使用LC-MS/MS来定量假定释放的特定三肽。用CHAPSO重组γ-分泌酶系统，我们证实Aβ49通过连续释放两个或三个三肽转化为Aβ43/40，而Aβ48通过连续释放两个三肽或这些三肽加上一个额外的四肽转化为Aβ42/38。

项目成果

Equimolar production of amyloid s-protein and APP intracellular domain from s-carboxyl terminal fragment by γ-secretase.

γ-分泌酶从 s-羧基末端片段等摩尔产生淀粉样蛋白 s-蛋白和 APP 胞内结构域。

• 发表时间: 2006
• 期刊: J Biol Chem 281
• 作者: Kakuda N;Funamoto S;Yagishita S;Takami M;Osawa S;Dohmae N;Ihara Y
• 通讯作者: Ihara Y

DAPT-induced intracellular accumulations of longer amyloid β-proteins: Further implications for the mechanism of intramembrane cleavage by γ-secretase.

DAPT 诱导的较长淀粉样 β 蛋白的细胞内积累：对 γ 分泌酶膜内裂解机制的进一步影响。

• 发表时间: 2006
• 期刊: Biochemistry 45
• 作者: Yagishita S;et. al.
• 通讯作者: et. al.

Collapsin response mediator protein-2 regulates neurite formation by modulating tubulin GTPase activity

• DOI: 10.1016/j.cellsig.2009.07.017
• 发表时间: 2009-12-01
• 期刊: CELLULAR SIGNALLING
• 影响因子: 4.8
• 作者: Chae, Young Chan;Lee, Sukmook;Ryu, Sung Ho
• 通讯作者: Ryu, Sung Ho

How gamma cleavage and epsilon cleavage are related to each other?

γ 裂解和 epsilon 裂解如何相互关联？

• 发表时间: 2007
• 作者: Miyashita A;et.al.;Ihara Y;Ihara Y
• 通讯作者: Ihara Y

g-Secretase : Successive tri- and tetrapeptide release from the transmembrane domain of βCTF

g-分泌酶：从βCTF的跨膜结构域连续释放三肽和四肽

• 发表时间: 2009
• 期刊: J Neurosci 29
• 作者: Takami M;et al
• 通讯作者: et al