Ca^<2+> channelplexes : assembly in the membrane and physiological significance

Ca^<2> 通道复合体：膜中的组装和生理意义

• 批准号: 17081011
• 负责人: MORI Yasuo
• 金额: $ 48.96万
• 依托单位: Kyoto University
• 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-17081011/
• 关键词: Ca^<2+>チャネル; 分子複合体; 膜分子集積; シグナル伝達; バイオセンサー; カルシウムチャネル

Ca^<2+> as a second messenger controls a wide variety of biological responses and contributes to formation of tissues such as bones, thereby playing a central role in regulating "homeostasis" at whole body, tissue, and cell levels. In my research, I have focused on voltage-dependent Ca^<2+> channels (VDCCs) and transient receptor potential (TRP) channels to aim at understanding mechanisms, that underlie formation and assembly at the biomembrane of Ca^<2+> channel protein complexes (Ca^<2+> channelplexes), and their physiological significance. Firstly, I have unveiled several unique activation mechanisms, that regulate cellular signal transduction for TRP Ca^<2+>-permeable caion channels. Secondly, I have demonstrated that channel proteins act not only as Ca^<2+>-permeating apparatus but also as assembly centers for receptors, signal-regulating proteins, and scaffolding proteins. Thirdly, important roles of Ca^<2+> channel protein complexes via formation of feedback regulation pathways in signal transduction have been demonstrated. Finally, I have also shown physiological significance of Ca^<2+> channelplexes at tissue levels. TRPC3 channelplexes in B lymphocyte activation and P/Q type VDCCplexes in presynaptic vesicle fusion are examples of the outcome of this study. Thus, my study clarifies how individual Ca^<2+> channels play roles in unique cellular responses.

Ca^2+作为第二信使，控制着多种生物反应，并有助于骨等组织的形成，从而在全身、组织和细胞水平上调节“体内平衡”中发挥核心作用。在我的研究中，我专注于电压依赖性Ca^<2+>通道（VDCC）和瞬时受体电位（TRP）通道，旨在了解Ca^<2+>通道蛋白复合物（Ca^<2 +> channelplexes）在生物膜上形成和组装的机制及其生理意义。首先，我揭示了几种独特的激活机制，它们调节TRP Ca^<2+>渗透性离子通道的细胞信号转导。其次，我已经证明了通道蛋白不仅作为Ca^2+渗透器，而且作为受体、信号调节蛋白和支架蛋白的组装中心。第三，Ca^<2+>通道蛋白复合物通过形成反馈调节通路在信号转导中的重要作用已被证实。最后，我还展示了组织水平上Ca^2+通道复合物的生理意义。B淋巴细胞活化中的TRPC 3通道复合体和突触前囊泡融合中的P/Q型VDCC复合体是本研究结果的例子。因此，我的研究阐明了单个Ca^<2+>通道在独特的细胞反应中如何发挥作用。

项目成果

Tetrameric Orail is a teardrop-shaped molecule with a long, tapered cytoplasmic domain.

四聚体 Orail 是一种泪滴状分子，具有长而锥形的细胞质结构域。

• 发表时间: 2009
• 期刊: J. Biol. Chem. 284
• 作者: Maruyama Y;Ogura T;Mio K;Kato K;Kaneko T;Kiyonaka S;Mori Y;Sato C.
• 通讯作者: Sato C.

RIM1 confers sustained activity and neurotransmitter vesicle anchoring to presynaptic Ca^(2+)channels.

RIM1 赋予突触前 Ca^(2 ) 通道持续的活性和神经递质囊泡锚定。

• 发表时间: 2007
• 期刊: Nat.Neurosci 10
• 作者: Ono K.;et al.;Kiyonaka S
• 通讯作者: Kiyonaka S

Comprehensive analysis of the ascidian genome reveals novel insights into the molecular evolution of ion channel genes

• DOI: 10.1152/physiolgenomics.00229.2004
• 发表时间: 2005-08-11
• 期刊: PHYSIOLOGICAL GENOMICS
• 影响因子: 4.6
• 作者: Okamura, Y;Nishino, A;Mori, Y
• 通讯作者: Mori, Y

A pathogenic C-terminus-truncated Polycistin-2 mutant enhances receptor-activated Ca^<2+> entry via association with TRPC3 and TRPC7.

致病性C-末端截短的Polycistin-2突变体通过与TRPC3和TRPC7结合增强受体激活的Ca 2+ 进入。

• 发表时间: 2009
• 期刊: J. Biol. Chem. 284
• 作者: Miyagi K;Kiyonaka S;Yamada K;Miki T;Mori E;Kato K;Numata T;Sawaguchi Y;Numaga T;Kimura T;Kanai Y;Kawano M;Wakamori M;Nomura H;Koni I;Yamagishi M;Mori Y.
• 通讯作者: Mori Y.

TRPM7 a possible extracellular divalent cati on sensor in hippocampal neurons.

TRPM7 是海马神经元中可能的细胞外二价阳离子传感器。

• 发表时间: 2007
• 期刊: Proc. Natl. Acad. Sci. USA 104
• 作者: Wei W-L;Olah ME;Czerwinska E;Czerwinski W;Mori Y;Orser BA;Xiong Z-G;Jackson MF;Tymianski M;MacDonald JF
• 通讯作者: MacDonald JF