The regulatory mechanisms and the physiological significance of SNAP-25 phosphorylation in mouse brain.

小鼠脑中SNAP-25磷酸化的调控机制及生理意义。

• 批准号: 24700385
• 负责人: YAMAMORI Saori
• 金额: $ 2.83万
• 依托单位: Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24700385/
• 关键词: リン酸化; 神経伝達物質放出; ストレス; SNAREタンパク質; プレシナプス; ドーパミン; SNAP-25; PKC; 脳

SNAP-25 plays a crucial role in neurotransmitter release by exocytosis. Protein kinase C phosphorylates SNAP-25 at Ser187, however the physiological significance of this phosphorylation event in brain function remains unclear. We found that SNAP-25 phosphorylation increased rapidly in the mouse brain following cold-water restraint stress. Both basal and stress-induced phosphorylation of SNAP-25 were high in stress-related brain regions and the extent of phosphorylation increased with increasing amounts of stress. Intravenous administration of adrenaline increased SNAP-25 phosphorylation, although stress-induced phosphorylation was still observed in adrenalectomized mice. These results indicate that SNAP-25 phosphorylation is regulated in a stress-dependent manner through both central and peripheral mechanisms. We also investigated SNAP-25 dephosphorylation, and found that protein phosphatase 2A participates in SNAP-25 dephosphorylation through Ca2+-dependent and independent mechanisms.

SNAP-25在通过胞吐作用释放神经递质中起关键作用。蛋白激酶C使SNAP-25在Ser 187处磷酸化，然而这种磷酸化事件在脑功能中的生理意义仍不清楚。我们发现SNAP-25磷酸化在冷水束缚应激后小鼠大脑中迅速增加。SNAP-25的基础和应激诱导的磷酸化在应激相关的脑区都很高，并且磷酸化的程度随着应激量的增加而增加。静脉注射肾上腺素增加SNAP-25磷酸化，尽管在肾上腺切除小鼠中仍然观察到应激诱导的磷酸化。这些结果表明，SNAP-25磷酸化是通过中枢和外周机制以应激依赖性方式调节的。我们还研究了SNAP-25的去磷酸化，发现蛋白磷酸酶2A通过Ca 2+依赖性和非依赖性机制参与SNAP-25的去磷酸化。

项目成果

Stress-induced phosphorylation of SNAP-25.

应激诱导的 SNAP-25 磷酸化。

• DOI: 10.1016/j.neulet.2013.12.044
• 发表时间: 2014
• 期刊: Neurosci Letter
• 作者: Yamamori S;Sugaya D;Iida Y;Kokubo H;Itakura M;Suzuki E;Kataoka M;Miyaoka H;Takahashi M
• 通讯作者: Takahashi M

PKC-dependent phosphorylation of SNAP-25 is essential for the positive regulation of dopamine release in mouse brain。

SNAP-25 的 PKC 依赖性磷酸化对于小鼠大脑中多巴胺释放的正向调节至关重要。

• 作者: Saori Yamamori;Suguru Kanno and Masami Takahashi
• 通讯作者: Suguru Kanno and Masami Takahashi

Protein phosphatase 2A dephosphorylates SNAP-25 through two distinct mechanisms in mouse brain synaptosomes

• DOI: 10.1016/j.neures.2013.01.002
• 发表时间: 2013-03-01
• 期刊: NEUROSCIENCE RESEARCH
• 影响因子: 2.9
• 作者: Iida, Yuuki;Yamamori, Saori;Takahashi, Masami
• 通讯作者: Takahashi, Masami