Regulation of cortical dendrite development by Rap1 signaling
Regulation of cortical dendrite development by Rap1 signaling
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DOI：
10.1016/j.mcn.2004.08.012
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发表时间：
2005-02-01
影响因子：
3.5
通讯作者：
Ghosh, A
中科院分区：
文献类型：
--
作者：
Chen, YC;Wang, PY;Ghosh, A
Rap1是一种小的GTP结合蛋白，参与细胞内信号传导和细胞骨架控制。在这里，我们表明，Rap1在大鼠皮层神经元中表达，并在树突发育中起着至关重要的作用。抑制Rap1信号无论是通过表达显性负突变的Rap1或Rap1GAP在皮层神经元减少树突的复杂性。相反，Rap1的组成型活性突变体（Rap1V12）的表达诱导树突状细胞的生长和分支。膜去极化通过钙离子内流诱导树突生长，通过cAMP和cGMP信号传导导致Rapt的快速激活。CREB依赖性机制参与去极化诱导的皮层神经元树突生长。Rap1功能有助于去极化诱导CREB激活，抑制CREB抑制Rap1V12诱导的树突状细胞生长。这些观察确定Rap1作为CREB依赖性转录和树突发育的钙调节的关键介质。(C)2004年由Elsevier Inc.出版
Rap1 is a small GTP-binding protein that has been implicated in intracellular signaling and cytoskeletal control. Here, we show that Rap1 is expressed in rat cortical neurons and plays a critical role in dendritic development. Inhibition of Rap1 signaling either by expressing dominant negative mutant of Rap1 or Rap1GAP in cortical neurons reduced dendritic complexity. In contrast, expression of a constitutively active mutant of Rap1 (Rap1V12) induced dendritic growth and branching. Membrane depolarization, which induces dendritic growth via calcium influx, led to a rapid activation of Rapt via cAMP and cGMP signaling. A CREB-dependent mechanism is involved in depolarization-induced dendritic growth in cortical neurons. Rap1 function contributed to depolarization induced CREB activation, and inhibition of CREB suppressed dendritic growth induced by Rap1V12. These observations identify Rap1 as a key mediator of calcium regulation of CREB-dependent transcription and dendritic development. (C) 2004 Published by Elsevier Inc.