A study on the molecular hasis of intracellular Ca^<2+> stores

细胞内Ca^<2>储存分子机制的研究

• 批准号: 15109005
• 负责人: TAKESHIMA Hiroshi
• 金额: $ 72.72万
• 依托单位: Kyoto University (2006-2007)Tohoku University (2003-2005)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (S)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15109005/
• 关键词: Ca^<2+> release; endoplasmic reticulum; junctophilin; Calumin; ryanodine receptor; TRIC channel; junctional membrane complex; channel crosstalk; カウンターイオン; K+チャネル; Ca2+依存性K+チャネル; 神経可塑性; 後過分極; カルシウムストア; 興奮性細胞; 筋収縮; Ca2+ストア; Ca2+結合タンパク質; ジャ

Cell signaling requires efficient Ca^<2+> mobilization from intracellular stores through Ca^<2+> release channels, as well as predicted counter movement of ions across the sarcoplasmic/endoplasmic reticulum (SR/ER) membrane to balance the transient negative potential generated by Ca^<2+> release^<1-7>. Ca^<2+> release channels were cloned more than 15 years ago^<8,9>, whereas molecular identity of putative counterion channels remains unknown. Here we report two TRIC (trimeric intracellular cation) channel subtypes that are differentially expressed on intracellular stores in animal cell types. TRIC subtypes contain three proposed transmembrane segments and form homo-trimers with a bullet-like structure. Electrophysiological measurements with purified TRIC preparations identify a monovalent cation-selective channel. In TRIC-knockout mice suffering embryonic cardiac failure, mutant cardiac myocytes display severe dysfunction in intracellular Ca^<2+> handling. The TRIO-deficient skeletal muscle SR shows reduced K+ permeability, as well as altered Ca^<2+> spark signaling and voltage-induced Ca^<2+> release. Therefore, TRIC channels correspond closely to the long-sought counter-ion channels that function in synchronization with SR/ER Ca^<2+> release.

细胞信号传递需要通过钙释放通道从细胞内储藏中有效地动员钙，以及预测到跨肌质/内质网(SR/ER)膜的离子反向移动，以平衡由钙释放产生的瞬时负电位。钙离子释放通道早在15年前就被克隆了，而推测的反离子通道的分子同一性尚不清楚。在这里，我们报告了在动物细胞类型的细胞内存储上差异表达的两种TRIC(三聚体细胞内阳离子)通道亚型。TRICE亚型包含三个跨膜片段，形成具有子弹样结构的同源三聚体。用纯化的电针制剂进行的电生理测量确定了一价阳离子选择性通道。在遭受胚胎心力衰竭的基因敲除小鼠中，突变的心肌细胞在细胞内钙处理方面表现出严重的功能障碍。三者缺陷性骨骼肌SR表现为K+通透性降低，同时改变了钙离子火花信号和电压诱导的钙离子释放。因此，TRIC通道与长期寻找的反离子通道密切对应，这些反离子通道与SR/ER钙离子释放同步发挥作用。

项目成果

Nishi ほか4名: "Coexpression of junctophilin type 3 and type 4 in brain"Mol. Brain Res.. 110. 102-110 (2003)

Nishi 等 4 人：“大脑中 3 型和 4 型亲细胞蛋白的共表达”Mol Brain Res.. 110. 102-110 (2003)

Impaired Ca2+ store functions in skeletal and cardiac muscle cells from sarcalumenin-deficient mice

• DOI: 10.1074/jbc.m406618200
• 发表时间: 2005-02-04
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Yoshida, M;Minamisawa, S;Takeshima, H
• 通讯作者: Takeshima, H

Bichemical and biophysical characterization of mitsugumin 33

Mitsugumin 33 的生化和生物物理表征

• 发表时间: 2008
• 作者: Younis;N.;Okuda;K.;Nishi;M.;Yamazaki;T.;Aoki;S.;Carter,
• 通讯作者: Carter,

Calumin, a novel Cat^<2+>-binding transmembrane protein on the endoplasmic reticulum.

Calumin，一种内质网上的新型Cat^2结合跨膜蛋白。

• 发表时间: 2007
• 期刊: Cell Calcium 42
• 作者: Zhang M.;他8名
• 通讯作者: 他8名

Enhanced resistance to fatigue and altered calcium handling properties of sarcalumenin knockout mice.

肌钙蛋白敲除小鼠的抗疲劳能力增强并改变钙处理特性。

• 发表时间: 2005
• 期刊: Physiol.Genomics 23
• 作者: Ikeno M;Suzuki N;Hasegawa Y;Okazaki T.;寺崎哲也;田中 誠司;Zhao ほか8名
• 通讯作者: Zhao ほか8名