Molecular mechanisms underlying the generation of spatiotemporal patterns of cytoplasmic calcium

细胞质钙时空模式产生的分子机制

• 批准号: 14580667
• 负责人: MICHIKAWA Takayuki
• 金额: $ 2.3万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14580667/
• 关键词: calcium signal; inositol trisphosphate; molecular cloning; receptor; intracellular localization; endplasmic reticulum; ligand binding; ionic channel; カルシウムチャネル; システイン

Inositol 1,4,5-trisphosphate (IP_3) is a second messenger generated by the phosphatidylinositol signaling cascade response to hormones, neurotransmitters, and growth factors and causes Ca^<2+> release from intracellular stores by binding to the IP_3 receptor (IP_3R), which is an IP_3-gated intracellular Ca^<2+> release channel. Ca^<2+> release in the cytoplasm occurs in complex spatial and temporal patterns, such as Ca^<2+> waves and Ca^<2+> oscillations, and regulates many cellular responses, including fertilization, muscle contraction, secretion, cell growth, differentiation, apoptosis, and synaptic plasticity. In this research, we isolated cDNAs encoding type 2 and type 3 IP_3R from mouse lung and found that each type of receptor binds IP_3 with different affinity and cooperativity. We also found that stimulation with ATP of Ca^<2+> ionophore induced cluster formation of all three types of mouse IP_3R expressed in COS-7 cells and that the size and shape of stimulus-induced clusters differ among the three types of IP_3R. The diversity of responsiveness to IP_3 and the intracellular distribution observed among the three IP_3R types may contribute to the generation of the complex spatiotemporal patterns of cytoplasmic Ca^<2+>.

三磷酸肌醇（Inositol 1，4，5-trisphosphate，IP_3）是磷脂酰肌醇（phosphatidylinositol，PI）信号级联反应产生的第二信使，通过与IP_3受体（IP_3 receptor，IP_3R）结合，引起细胞内Ca ^2+释放。细胞质中的Ca^2+释放以复杂的空间和时间模式发生，如Ca^2+波和Ca^2+振荡，并调节许多细胞反应，包括受精、肌肉收缩、分泌、细胞生长、分化、凋亡和突触可塑性。本研究从小鼠肺组织中分离了编码2型和3型IP_3受体的cDNA，发现每种受体与IP_3的结合具有不同的亲和力和协同性。我们还发现，用ATP刺激Ca^<2+>离子载体可诱导COS-7细胞中表达的三种类型的小鼠IP_3 R形成簇，并且刺激诱导的簇的大小和形状在三种类型的IP_3 R中不同。IP_3受体对IP_3反应的多样性和胞内分布的多样性可能是导致胞浆Ca^<2+>复杂时空分布的原因。

项目成果

道川貴章: "感覚器官と脳内情報処理 第4章4-6人工脂質重膜"共立出版. 12 (2002)

Takaaki Michikawa：“感觉器官和大脑信息处理第4章4-6人工脂质膜”Kyoritsu Shuppan 12（2002）。

Hisatsune C: "Regulation of TRPC6 channel activity by tyrosine phosphorylation"J.Biol.Chem.. 印刷中.

Hisatsune C：“通过酪氨酸磷酸化调节 TRPC6 通道活性”J.Biol.Chem.. 正在出版。

Cluster formation of inositol 1,4,5-trisphosphate receptor requires its transition to open state

• DOI: 10.1074/jbc.m405469200
• 发表时间: 2005-02-25
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Tateishi, Y;Hattori, M;Mikoshiba, K
• 通讯作者: Mikoshiba, K

Critical regions for activation gating of the inositol 1,4,5-triphosphate receptor

肌醇 1,4,5-三磷酸受体激活门控的关键区域

• 发表时间: 2003
• 期刊: J.Biol.Chem. 278
• 作者: Uchida K.

Bosanac, I.: "Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with IP_3"Nature. 420. 696-700 (2002)

Bosanac，I.：“与 IP_3 复合的肌醇 1,4,5-三磷酸受体结合核心的结构”《自然》。