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

神经营养蛋白和各种生长因子在大脑中表达，并在发展中和成年大脑中起重要作用。最近的研究表明，各种营养因素涉及调节学习和记忆的突触可塑性，但是，精确的机制仍然晦涩难懂。为了阐明营养因子介导的突触前功能的调节，表皮生长因子（EGF）和胰岛素样生长因子-1（IGF-1）对神经递质释放的影响，在克隆大鼠pheochromocytoma PC12细胞中研究了神经递质释放。 EGF和IGF-1的简短处理以浓度依赖性的方式从PC12细胞中释放出依赖性的Ca^<2+>依赖性多巴胺（DA）。 EGF激活了有丝分裂原激活的蛋白激酶（MAPK）和磷脂酰肌醇3-激酶（PI3-激酶）途径，以及通过引人注目的对比度释放DA释放的增强，IGF igf…更多。由MAPK激酶抑制剂。蛋白激酶B（PKB）的EGFP标记的pH结构域与磷脂酰肌醇3,4-双磷酸和磷脂酰肌醇3,4,5-三磷酸的结合，在PC12细胞中表达的PC12细胞在PC12细胞中表达，并通过EGF或神经生长（NGF）翻译为NGF，并均转化为NGF）。 PI3-激酶的潜在抑制剂。相比之下，IGF-1诱导EGFP-PKB-PH的明显重新分布。 EGF以及NGF诱导了肌动蛋白细胞骨架的重组，尤其是在细胞过程中，IGF-1仅诱导了略有变化。用EGF或NGF处理后，将超过9种细胞蛋白磷酸化，PKB（PKB）的下游酶（PI3-激酶的下游酶），但是通过IGF-1磷酸化了不同的蛋白质。这些结果表明，PI3-激酶通过两种不同的机制参与了神经递质释放的增强。较少的

项目成果

Negative regulation of neurotransmitter release by calpain : a posssible involvement of specific SMAP-25 cleavage.

钙蛋白酶对神经递质释放的负调节：可能涉及特定的 SMAP-25 裂解。

• 发表时间: 2005
• 期刊: J Neurochem 94
• 作者: Shimizu S;Inamura M;Sadataka T;Shimizu S;Inamura M;Sadataka T;Shunichi Shimizu;Ohnishi H;Ando K
• 通讯作者: Ando K

板倉 誠: "神経伝達物質の放出機構"実験医学増刊 脳・神経研究2004. 21. 2357-2360 (2003)

板仓诚：《神经递质释放机制》实验医学特刊脑与神经研究2004.21.2357-2360(2003)

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

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