Regulation of the Na+/H+ exchanger and signal transduction

Na /H 交换器和信号转导的调节

• 批准号: 09680642
• 负责人: WAKABAYASHI Shigeo
• 金额: $ 2.11万
• 依托单位: National Cardiovascular Center Research Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09680642/
• 关键词: Na+; H+ exchanger; volume regulation; calcineurin homologue protein; calmodulin; Na^+; H^+交換輸送体; 細胞容積; カルシニューリン類似タンパク質; Ca^<2+>交換輸送体; 増殖因子; プロテインキナーゼC; 細胞内PH; 細胞内Ca^<2+>; 情報伝達

The Na/He exchanger (NHE) is an important regulator for intracellular pH (pH), C* volume, and transepithelial Na^+ transport. It exists in virtually all cells with cell ty* dependent pattern of isoform expression. Among six known isoforms of NHE, a ubiquito* isoform NHE1 is known to be rapidly activated in response to a variety of extracellul* stimuli ranging from growth factors to mechanical stimuli such as hyperosmotic stress a* cell spreading. Some accessory regulatory factors has been suggested to be involved in * regulation of NHE1. Galmodulin is the first identified regulatory factor that is involved Ca^<2+>-induced activation of NHE1. Recently, the calcineurin B homologous protein (CHP) h* been cloned as a candidate for such regulatory factors of NHE1. In recent two years, w* tried to identify CHP binding domain within NHE1. A cytoplasmic region of aa 515-530 w* identified as a strong CHP-binding domain. However, we have not yet determine t* precise role of CHP in the regulation of NHE1. We also tried to identify an important regi* of NHE for volume regulation and found that the first extracellular loop is a critical region f* positive or negative response to volume change in NHE isoforms.

Na/He交换器（NHE）是细胞内pH（pH）、C* 容量和跨上皮Na^+转运的重要调节器。它存在于几乎所有具有细胞类型依赖性亚型表达模式的细胞中。在六种已知的NHE亚型中，已知泛素 * 亚型NHE 1响应于多种细胞外刺激而被快速激活，所述细胞外刺激范围从生长因子到机械刺激，例如高渗应激和细胞扩散。一些辅助调节因子被认为参与了NHE 1的调节。Galmodulin是第一个被鉴定的参与Ca^2+诱导的NHE 1活化的调节因子。最近，钙调神经磷酸酶B同源蛋白（CHP）已被克隆作为NHE 1的这种调节因子的候选者。近两年来，我们试图鉴定NHE 1中的CHP结合结构域。aa 515-530 w* 的胞质区域被鉴定为强CHP结合结构域。然而，我们尚未确定CHP在NHE 1调节中的确切作用。我们还试图确定一个重要的区域NHE的容量调节，并发现第一个细胞外环是一个关键区域的NHE亚型的体积变化的积极或消极的反应。

项目成果

Wakabayashi, S., Ikeda, T., Kobayashi, Y., Iwamoto, T., and Shigekawa, M.: "The Na+/H+ exchanger and volume regulation" In“Cell volume regulation : The moledular mechanism and volume sensing mashinery", edited. by Y. Okada, Elsevier Publishers.167-171 (19

Wakabayashi, S.、Ikeda, T.、Kobayashi, Y.、Iwamoto, T. 和 Shigekawa, M.：“Na+/H+ 交换器和体积调节”，In“细胞体积调节：分子机制和体积传感机械” ，由 Y. Okada 编辑，Elsevier Publishers.167-171 (19

Iwamoto,T.et al.: "Na^+/Ca^<2+> exchanger overexpression impairs calcium signaling in fibroblasts" Eur.J.of Cell Biol.76. 228-236 (1998)

Iwamoto,T.et al.：“Na^/Ca^2交换器过度表达损害成纤维细胞中的钙信号传导”Eur.J.of Cell Biol.76。

S.Wakabayashi et al.: "Calmuolnlin-Binding Antoinhibitory Domain Conbols "pH-sensing" in the Na^+/H^+ exchanger. NHE1 rhnugh Sejnence-Specific Enteroction." Biochemistry. 36(42). 12854-12861 (1997)

S.Wakabayashi 等人：“Calmuolnlin 结合抗抑制结构域 Conbols Na^ /H^ 交换器中的“pH 感应”。NHE1 rhnugh Sejnence-Specific Enteroction。”

Iwamoto, T., Wakabayashi, S., Imagawa, T., and Shigekawa, M.: "Na^+/Ca^<2+> exchanger overexpression impairs calcium signaling in fibroblasts : Inhibition of the (Ca^<2+>)increase at the cell periphery and retardation of cell adhesion." Eur.J.of Cell Biol

Iwamoto, T.、Wakabayashi, S.、Imakawa, T. 和 Shigekawa, M.：“Na^ /Ca^<2 > 交换器过度表达会损害成纤维细胞中的钙信号传导：抑制 (Ca^<2 >) 增加

Ikeda,T.Wakabayashi,S Shigekawa,M.: "Mechanism of inhibision Na^+/H^+ exchanger (NHE1) by Arp dipletion" In “Progress is experimental cordiology"Kluwer Academic Publishers,Boston. 189-197 (1998)

Ikeda, T. Wakabayashi, S Shigekawa, M.：“Arp dipletion 抑制 Na^+/H^+ 交换器 (NHE1) 的机制”，《进步是实验性心脏病学》，Kluwer 学术出版社，波士顿 189-197（ 1998）