Regulation of cortical dendrite development by Rap1 signaling

被引：43

作者：

Chen, YC

Wang, PY

Ghosh, A ^{[1
]}

机构：

[1] Univ Calif San Diego, Neurobiol Sect, Div Biol, La Jolla, CA 92093 USA

[2] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA

来源：

MOLECULAR AND CELLULAR NEUROSCIENCE | 2005年 / 28卷 / 02期

关键词：

D O I：

10.1016/j.mcn.2004.08.012

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：215 / 228

页数：14

共 58 条

[1] GTK, a Src-related tyrosine kinase, induces nerve growth factor-independent neurite outgrowth in PC12 cells through activation of the Rap1 pathway -: Relationship to Shb tyrosine phosphorylation and elevated levels of focal adhesion kinase [J].