The Rac1-GEF Tiam1 couples the NMDA receptor to the activity-dependent development of dendritic arbors and spines

被引：303

作者：

Tolias, KF

Bikoff, JB

Burette, A

Paradis, S

Harrar, D

Tavazoie, S

Weinberg, RJ

Greenberg, ME ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Neurobiol Program, Childrens Hosp, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA

[4] Univ N Carolina, Dept Cell & Dev Biol, Chapel Hill, NC 27599 USA

[5] Univ N Carolina, Ctr Neurosci, Chapel Hill, NC 27599 USA

来源：

NEURON | 2005年 / 45卷 / 04期

关键词：

D O I：

10.1016/j.neuron.2005.01.024

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：525 / 538

页数：14

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