Study of the Molecular Structure and Function of IP_3 Receptor/Ca^<2+> Release Channel

IP_3受体/Ca^<2>释放通道的分子结构与功能研究

基本信息

  • 批准号:
    08459009
  • 负责人:
  • 金额:
    $ 6.08万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
  • 财政年份:
    1996
  • 资助国家:
    日本
  • 起止时间:
    1996 至 1997
  • 项目状态:
    已结题

项目摘要

1. We found that the "core" region for IP3 binding in the type 1 IP3 receptor (IP3R) is located in the N-terminal region from 225 to 578 a.a., and that within this region, at least three basic amino acids (Arg-265, Lys-508, Arg-511) are essential for binding to the negatively-charged IP3 molecule.2. The IP3 binding activity of type 1 and 3 expressed in Sf9 cells displayd an opposite dependency to increasing Ca2+ ; affinity for IP3 is decreased in type 1 (EC50=100nM Ca2+), whereas increased in type 3 (872nM). IP3 sensitivity in IP3-induced Ca2+ release (IICR) of type 3 was lower than that of type 1 (EC50=358nM vs 226nM IP3). These suggest that cytosolic Ca2+ as well aw IP3 concentrations are involved in type-specific IICR.3. Type 2 has been thought to be "high affinity" IP3R.However, liver IP3R of type 1 knock-out mice, in which type 2 predominates, showed a similar IP3 sensitivity in IICR as type 1.4. By expressing a fusion protein with green fluorescent protein (GFP) in Xenopus oocyte … More s, we showed that the expressed C-terminal region including a putative channel region is sufficient for the ER localization and the tetramer formation.5. We established transgenic mouse lines carrying beta-gal gene controlled by type 1 gene promoter, and analyzed the gene expression by detecting beta-gal activity in the nervous system. We identified two cerebellum-specific regions in this promoter ; one is a positive element from -398--295, the other is an E-box-like box I from -334--318. We also determined the primary structure of type 2 gene promoter, and found the presence of multiple transcription initiation sites.6. By immunohistochemistry of rat kidney, we localized type 1 IP3R to vascular smooth muscle cells and mesangial cells, type 2 to intercalated cells of the collecting duct, and type 3 to vascular smooth muscle cells, mesangial cells and principal cells of the cortical collecting duct. Intracellularly, type 1 and 2 are located throughout the cytoplasm, whereas type 3 is restricted to the basolateral side, suggesting the differential Ca2+ signaling due to the polarization in the subcellular localization of distinct types. Less
1. 我们发现1型IP3受体(IP3R)中IP3结合的“核心”区域位于N端区域225至578个氨基酸,并且在该区域内,至少有3个碱性氨基酸(Arg-265、Lys-508、Arg-511)对于与带负电荷的IP3分子的结合是必需的。2. Sf9 细胞中表达的 1 型和 3 型 IP3 结合活性表现出与增加 Ca2+ 相反的依赖性; 1 型中 IP3 的亲和力降低 (EC50=100nM Ca2+),而 3 型中 IP3 的亲和力增加 (872nM)。 3型的IP3诱导Ca2+释放(IICR)的IP3敏感性低于1型(EC50=358nM vs 226nM IP3)。这些表明胞质 Ca2+ 以及 aw IP3 浓度与类型特异性 IICR.3 有关。 2型被认为是“高亲和力”IP3R。然而,1型敲除小鼠(其中2型占主导地位)的肝脏IP3R在IICR中表现出与1.4型相似的IP3敏感性。通过在非洲爪蟾卵母细胞中表达带有绿色荧光蛋白(GFP)的融合蛋白,我们发现表达的C端区域(包括假定的通道区域)足以用于内质网定位和四聚体形成。5.我们建立了携带由1型基因启动子控制的β-gal基因的转基因小鼠品系,并通过检测神经系统中的β-gal活性来分析基因表达。我们在该启动子中鉴定了两个小脑特异性区域;一个是-398--295的正元素,另一个是-334--318的类似E盒的盒子I。我们还确定了2型基因启动子的一级结构,发现存在多个转录起始位点。 6.通过大鼠肾脏的免疫组织化学,我们将1型IP3R定位于血管平滑肌细胞和系膜细胞,2型定位于集合管的嵌入细胞,3型定位于血管平滑肌细胞、系膜细胞和皮质集合管的主细胞。在细胞内,1 型和 2 型遍布整个细胞质,而 3 型仅限于基底外侧,这表明由于不同类型的亚细胞定位中的极化而导致不同的 Ca2+ 信号传导。较少的

项目成果

期刊论文数量(47)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Li M: "Differential cellular expression of three types of inositol 1,4,5-trisphosphate receptor in rat gastrointestinal epithelium." Biomed.Res.17. 45-51 (1996)
Li M:“大鼠胃肠道上皮细胞中三种类型肌醇1,4,5-三磷酸受体的差异细胞表达。”
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
古市貞一: "発生分化とCa^<2+>" Clinical Neuroscience. 14. 28-29 (1996)
Teiichi Furuichi:“发育分化和 Ca^<2+>”临床神经科学 14. 28-29 (1996)。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Michikawa, T.: "Inositol 1,4,5-trisphosphate receptors and calcium signaling" Critical Reviews in Neurobiology. 10. 39-55 (1996)
Michikawa, T.:“肌醇 1,4,5-三磷酸受体和钙信号传导”神经生物学评论。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Yoneshima H: "Ca^<2+> differentially regulates the ligand-affinity states of type 1 and type 3 inositol 1,4,5-trisphosphate receptors." Biochem.J.(印刷中).
Yoneshima H:“Ca^2+ 差异调节 1 型和 3 型肌醇 1,4,5-三磷酸受体的配体亲和状态。”(正在出版)。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Furutama D: "Functional expression of the type 1 inositol 1,4,5-trisphosphate receptor promoter-lacZ.fusion gene in transgenic mice." J.Neurochem.66. 1793-1801 (1996)
Furutama D:“转基因小鼠中 1 型肌醇 1,4,5-三磷酸受体启动子-lacZ.融合基因的功能表达。”
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  • 影响因子:
    0
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FURUICHI Teiichi其他文献

FURUICHI Teiichi的其他文献

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{{ truncateString('FURUICHI Teiichi', 18)}}的其他基金

Study on the molecular mechanisms underlying CAPS-mediated exocytosis of dense-core vesicles containing BDNF and catecholamine
CAPS介导的BDNF和儿茶酚胺致密核囊泡胞吐作用的分子机制研究
  • 批准号:
    23300137
  • 财政年份:
    2011
  • 资助金额:
    $ 6.08万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Study of Molecular Organization of Mouse Cerebellum
小鼠小脑分子组织的研究
  • 批准号:
    13308047
  • 财政年份:
    2001
  • 资助金额:
    $ 6.08万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
Study of the Structure-Function of IPィイD23ィエD2 Receptor/CaィイD12+ィエD1 Release Channel and IPィイD23ィエD2/CaィイD12+ィエD1 Signaling
IPD23D2受体/CaD12+D1释放通道结构功能及IPD23D2/CaD12+D1信号传导的研究
  • 批准号:
    10490007
  • 财政年份:
    1998
  • 资助金额:
    $ 6.08万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Study of the IP_3 receptor family and its diverse roles in various physiological functions
IP_3受体家族及其在多种生理功能中的多种作用的研究
  • 批准号:
    05455006
  • 财政年份:
    1993
  • 资助金额:
    $ 6.08万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)

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    2312149
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    2023
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Next-generation biophysical models for RNA dynamics, ligand binding, and catalysis
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增强 Phyre 蛋白质建模资源:配体结合的预测和错义变体的影响
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SBIR 第一阶段:识别蛋白质-配体结合位点的非线性光学方法
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