Dual role of DENN/MADD (Rab3GEP) in neurotransmission and neuroprotection
Dual role of DENN/MADD (Rab3GEP) in neurotransmission and neuroprotection
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DOI：
10.1016/j.molmed.2004.08.002
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发表时间：
2004-10-01
影响因子：
13.6
通讯作者：
Takai, Y
中科院分区：
文献类型：
--
作者：
Miyoshi, J;Takai, Y
DENN/MADD 是信号蛋白复合物的一个组成部分，定位于细胞质并通过使用不同的结合配偶体发挥多种功能。人 DENN/MADD 在物理上与大鼠 Rab3 GDP/GTP 交换蛋白 (Rab3GEP) 具有相同的死亡结构域蛋白。 DENN/MADD 在正常条件下调节 Rab3 小 G 蛋白的再循环，并在 Ca2+ 依赖性神经递质释放和胞吐作用中发挥重要作用。它还参与阻断细胞毒性应激条件下神经元细胞的凋亡。最近的研究支持 DENN/MADD 在神经保护中的重要作用：在受阿尔茨海默病影响的大脑中发现内源性 DENN/MADD 表达减少和促凋亡信号增强。
DENN/MADD is a component of a signalling protein complex that is localized to the cytosol and exerts multiple functions by using different binding partners. Human DENN/MADD is physically the same death-domain protein as rat Rab3 GDP/GTP exchange protein (Rab3GEP). DENN/MADD regulates the recycling of Rab3 small G proteins under normal conditions and has an essential role in Ca2+-dependent neurotransmitter release and exocytosis. It is also involved in blocking the apoptosis of neuronal cells under conditions of cytotoxic stress. Recent research supports an important role for DENN/MADD in neuroprotection: reduced endogenous DENN/MADD expression and enhanced pro-apoptotic signalling has been found in brains affected by Alzheimer's disease.