Rac1鸟嘌呤核苷酸交换因子Tiam1将N-甲基-D-天冬氨酸受体与树突棘和树突分支的活性依赖性发育联系起来。

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

作者信息

Tolias Kimberley F, Bikoff Jay B, Burette Alain, Paradis Suzanne, Harrar Dana, Tavazoie Sohail, Weinberg Richard J, Greenberg Michael E

机构信息

Neurobiology Program, Children's Hospital, Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA.

出版信息

Neuron. 2005 Feb 17;45(4):525-38. doi: 10.1016/j.neuron.2005.01.024.

DOI:10.1016/j.neuron.2005.01.024

PMID:15721239

Abstract

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.

摘要

N-甲基-D-天冬氨酸（NMDA）型谷氨酸受体在树突分支和棘突的活性依赖型发育及结构重塑中发挥关键作用。然而，将NMDA受体激活与树突形态变化联系起来的分子机制仍不清楚。我们报告称，Rac1鸟苷酸交换因子Tiam1存在于树突和棘突中，并且是它们发育所必需的。Tiam1与NMDA受体相互作用，并在NMDA受体刺激下以钙依赖的方式被磷酸化。用RNA干扰和Tiam1的显性干扰突变体阻断Tiam1功能表明，Tiam1通过诱导Rac1依赖的肌动蛋白重塑和蛋白质合成来介导NMDA受体对树突发育的影响。综上所述，这些发现定义了一种分子机制，通过该机制NMDA受体信号传导控制树突分支和棘突的生长及形态。