The Rac1-GEF Tiam1 couples the NMDA receptor to the activity-dependent development of dendritic arbors and spines
The Rac1-GEF Tiam1 couples the NMDA receptor to the activity-dependent development of dendritic arbors and spines
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DOI：
10.1016/j.neuron.2005.01.024
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发表时间：
2005-02-17
期刊：
影响因子：
16.2
通讯作者：
Greenberg, ME
中科院分区：
文献类型：
--
作者：
Tolias, KF;Bikoff, JB;Greenberg, ME
NMDA型谷氨酸受体在树突状乔木和棘的活性依赖性发育和结构重塑中起关键作用。然而，连接NMDA受体激活树突状形态的变化的分子机制仍然不清楚。我们报告说，Rac 1-GEF Tiam 1存在于树突和棘，并需要为他们的发展。Tiam 1与NMDA受体相互作用，并以钙依赖性方式磷酸化以响应NMDA受体刺激。用RNAi和Tiam 1的显性干扰突变体阻断Tiam 1功能表明Tiam 1通过诱导Rac 1依赖的肌动蛋白重塑和蛋白质合成介导NMDA受体对树突发育的影响。总之，这些发现定义了一个分子机制，NMDA受体信号控制的生长和形态的树突状乔木和刺。
NMDA-type glutamate receptors play a critical role in the activity-dependent development and structural remodeling of dendritic arbors and spines. However, the molecular mechanisms that link NMDA receptor activation to changes in dendritic morphology remain unclear. We report that the Rac1-GEF Tiam1 is present in dendrites and spines and is required for their development. Tiam1 interacts with the NMDA receptor and is phosphorylated in a calcium-dependent manner in response to NMDA receptor stimulation. Blockade of Tiam1 function with RNAi and dominant interfering mutants of Tiam1 suggests that Tiam1 mediates effects of the NMDA receptor on dendritic development by inducing Rac1-dependent actin remodeling and protein synthesis. Taken together, these findings define a molecular mechanism by which NMDA receptor signaling controls the growth and morphology of dendritic arbors and spines.