Regulatory mechanisms of neurotransmitter release by cytokine and growth factors.

细胞因子和生长因子释放神经递质的调节机制。

• 批准号: 15300127
• 负责人: TAKAHASHI Masami
• 金额: $ 10.69万
• 依托单位: Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15300127/
• 关键词: EGF; NGF; IGF-1; growth factor; neurotransmitter; exocytosis; microdomain; phospholipid; SNAP-25; 特異抗体; EFG; 神経伝達物質放出; PIP2; PIP5キナーゼ; 神経伝達物資放出; MAPキナーゼ; PI3キナーゼ

Neurotrophins and various growth factors are expressed in brain and play important roles both in developing and in adult brains. Recent studies indicate that various trophic factors involve in the regulation of synaptic plasticity underlying learning and memory, however, the precise mechanisms are still remained obscure. In order to elucidate molecular mechanisms of trophic factor-mediated regulation of presynaptic functions, effects of epidermal growth factor (EGF) and insulin-like growth factor-1 (IGF-1) on neurotransmitter release were studied in clonal rat pheochromocytoma PC12 cells. A brief treatment of EGF and IGF-1 enhanced Ca^<2+> dependent dopamine (DA) release from PC12 cells in concentration-dependent manners. EGF activated both mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3-kinase) pathways, and EGF-dependent enhancement of DA release was suppressed by a MAPK kinase inhibitor as well as by PI3-kinase inhibitors. By the striking contrast, IGF … More -1 activated PI3-kinase pathway but not MAPK pathway, and IGF-1-dependent enhancement was suppressed by PI3-kinase inhibitor but not by MAPK kinase inhibitor. EGFP-tagged PH domain of protein kinase B (PKB), which selectively bind to phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-triphosphate, expressed in PC12 cells was translocated to plasma membrane after treatments with either EGF or nerve growth factor (NGF), and the translocations were abolished by wortmannin, a potent inhibitor of PI3-kinase. By the contrast, no significant redistribution of EGFP-PKB-PH was induced by IGF-1. EGF as well as NGF induced reorganization of actin cytoskeleton especially in the tip of cell process, however, only slight change was induced by IGF-1. More than nine cellular proteins were phosphorylated by PKB, a downstream enzyme of PI3-kinase, after a treatment with either EGF or NGF, however different set of proteins were phosphorylated by IGF-1. These results indicate that PI3-kinase participates in the enhancement of neurotransmitter release by two distinct mechanisms. Less

神经营养因子和各种生长因子在脑内表达，并在发育和成人脑中发挥重要作用。最近的研究表明，多种营养因子参与了学习和记忆中突触可塑性的调节，但其确切的机制仍不清楚。为阐明营养因子调节突触前功能的分子机制，研究了表皮生长因子(EGF)和胰岛素样生长因子-1(IGF-1)对克隆性大鼠嗜铬细胞瘤PC12细胞神经递质释放的影响。EGF和IGF-1以浓度依赖的方式促进PC12细胞钙离子依赖性多巴胺(DA)的释放。EGF同时激活丝裂原活化蛋白激酶(MAPK)和磷脂酰肌醇3-激酶(PI3-K)通路，依赖EGF的DA释放的促进作用可被MAPK和PI3-K抑制剂所抑制。与之形成鲜明对比的是，igf…More-1激活PI3-K途径而不激活MAPK途径，PI3-激酶抑制剂抑制IGF-1依赖性增强，MAPK不抑制IGF-1依赖性增强。在PC12细胞中表达的EGFP标记的蛋白激酶B的PH域(PKB)选择性地与磷脂酰肌醇3，4-二磷酸和磷脂酰肌醇3，4，5-三磷酸结合，经EGF或神经生长因子(NGF)处理后被移位到质膜，这种移位可被PI3-激酶的有效抑制剂Wortmannin取消。相反，IGF-1对EGFP-PKB-PH无明显的再分布作用。EGF和NGF均可引起肌动蛋白细胞骨架的重组，尤其是在细胞突起的顶端，而IGF-1仅引起轻微的改变。经EGF或NGF处理后，超过9种细胞蛋白被PI3-激酶下游酶PKB磷酸化，而不同的一组蛋白被IGF-1磷酸化。这些结果表明，PI3-激酶通过两种不同的机制参与促进神经递质的释放。较少

项目成果

Quantal size of catecholamine release from rat chromatin cells is regulated by tonic activity of protein kinase A.

大鼠染色质细胞释放的儿茶酚胺的数量大小受蛋白激酶 A 的强直活性调节。

• 发表时间: 2004
• 期刊: Neurosci Lett 360
• 作者: Shimizu S;Inamura M;Sadataka T;Shimizu S;Inamura M;Sadataka T;Shunichi Shimizu;Ohnishi H;Ando K;Itakura M;Aoyagi K;Oishi Y;Ohnishi H;Ando K;Oishi Y;Hiroshi Ohnishi;Kosuke Ando;Makoto Itakura;Kyota Aoyagi;Yohei Oishi;Kosuke Ando;Makoto Itakura;Hiroshi Ohnishi;Koga T;Koga T
• 通讯作者: Koga T

Differential distributions of the Ca2+-dependent activator protein for secretion family proteins (CAPS2 and CAPS1) in the mouse brain

• DOI: 10.1002/cne.20947
• 发表时间: 2006-04-20
• 期刊: JOURNAL OF COMPARATIVE NEUROLOGY
• 影响因子: 2.5
• 作者: Sadakata, T;Itakura, M;Furuichi, T
• 通讯作者: Furuichi, T

Masami Takahashi: "New aspects of neurotransmitter release and exocytosis : Regulation of neurotransmitter release by phosphorylation."J.Pharmacolo.Sci.. 93. 41-45 (2003)

Masami Takahashi：“神经递质释放和胞吐作用的新方面：通过磷酸化调节神经递质释放。”J.Pharmacolo.Sci.. 93. 41-45 (2003)

神経伝達物質の放出機構

神经递质释放机制

• 发表时间: 2008
• 期刊: 日本生理学雑誌 70
• 作者: Sakisaka;T;持田澄子
• 通讯作者: 持田澄子

Quantal size of catecholamine release from rat chromaffin cells is regulated by tonic activity of protein kinase A

• DOI: 10.1016/j.neulet.2004.02.057
• 发表时间: 2004-04
• 期刊: Neuroscience Letters
• 影响因子: 2.5
• 作者: Takeshi Koga;Masami Takahashi