Mechanism and physiological role for generation of the carboxyl terminal fragment of the P/Q-type calcium channel

P/Q型钙通道羧基末端片段的产生机制和生理作用

• 批准号: 21590228
• 负责人: SAEGUSA Hironao
• 金额: $ 3.08万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21590228/
• 关键词: Cav2. 1,カルボキシ末端; プロテアーゼ; 脊髄小脳変性症6型; SCA6; Cav2.1; カルボキシ末端

Generation of Cav2. 1 carboxyl terminal tail(Cav2. 1CT) is thought to be causally related to spinocerebellar ataxia type 6, a hereditary neurological disease. Cav2. 1CT is generated by cleavage of the full-length Cav2. 1 protein. But the exact mechanism underlying the generation of Cav2. 1CT and the function of this CT fragment remain to be clarified. In the present study, I have tried to clarify the mechanism to generate the Cav2. 1CT from full-length Cav2. 1 protein. Also, I have studied the functional role of the Cav2. 1CT in some in vitro systems. As a result, the following molecules are candidates for the protease responsible for the Cav2. 1CT generation : caspase 6, cathepsin L, and calpain small subunit 1, but further studies are necessary to conclude this. Cav2. 1CT was found to be toxic to cells and it is possible that Cav2. 1CT possess transcription repressing activity

第二代Cav2。1个羧基末端尾（Cav2. 1CT）被认为与脊髓小脑共济失调6型（一种遗传性神经系统疾病）有因果关系。骑士2号。1CT通过全长Cav2的切割产生。1蛋白质。但是Cav2产生的确切机制。1CT及其功能尚不清楚。在本研究中，我试图阐明产生Cav2的机制。全长Cav2的1CT。1蛋白质。此外，我还研究了Cav2的功能作用。1CT在某些体外系统中。因此，以下分子是负责Cav2的蛋白酶的候选分子。1CT生成：半胱天冬酶6、组织蛋白酶L和钙蛋白酶小亚基1，但需要进一步研究得出结论。骑士2号。发现CT对细胞有毒，并且Cav2. 1CT具有转录抑制活性

项目成果

Down-regulation of heat shock transcription factor 1-heat shock 70kDa protein 1 A axis and increased caspase-dependent apoptosis in a cell model of spinocerebellar ataxia type 6 (SCA6)

脊髓小脑共济失调 6 型 (SCA6) 细胞模型中热休克转录因子 1-热休克 70kDa 蛋白 1 A 轴的下调和 caspase 依赖性细胞凋亡的增加

• 发表时间: 2009
• 作者: Li;L.
• 通讯作者: L.

Deficit of heat shock transcription factor 1-heat shock 70 kDa protein 1A axis determines the cell death vulnerability in a model of spinocerebellar ataxia type 6

• DOI: 10.1111/j.1365-2443.2009.01348.x
• 发表时间: 2009-11-01
• 期刊: GENES TO CELLS
• 影响因子: 2.1
• 作者: Li, Li;Saegusa, Hironao;Tanabe, Tsutomu
• 通讯作者: Tanabe, Tsutomu

Involvement of miRNA in the pathogenesis of spinocerebellar ataxiatype 6 (SCA6)

miRNA 参与脊髓小脑共济失调 6 型 (SCA6) 的发病机制

• 发表时间: 2011
• 作者: Wimardhani YS;Suniarti DF;Freisleben HJ;Wanandi SI;Ikeda MA;Tsutomu Tanabe(代表)
• 通讯作者: Tsutomu Tanabe(代表)

Down regulation of particular miRNAs is responsible for the cell death vulnerability of spinocerebellar ataxia type 6 (SCA6)

特定 miRNA 的下调导致脊髓小脑共济失调 6 型 (SCA6) 的细胞死亡脆弱性

• 发表时间: 2011
• 作者: Garcia M.L.;Rao M.V.;Fujimoto J.,Garcia V.B.;Shah S.B.;Crum J.;Gotow T.,Uchiyama Y.;Ellisman M.;Calcutt N.A.;Cleveland D.W.;Tsutomu Tanabe(代表)
• 通讯作者: Tsutomu Tanabe(代表)