Sonic hedgehog signaling regulates actin cytoskeleton via Tiam1-Rac1 cascade during spine formation
Sonic hedgehog signaling regulates actin cytoskeleton via Tiam1-Rac1 cascade during spine formation
复制标题
DOI：
10.1016/j.mcn.2010.07.006
复制
发表时间：
2010-12-01
影响因子：
3.5
通讯作者：
Kengaku, Mineko
中科院分区：
文献类型：
--
作者：
Sasaki, Nobunari;Kurisu, Junko;Kengaku, Mineko
Sonic hedgehog(Shh)通路在脊椎动物中枢神经系统(CNS)发育的几个过程中起着重要作用。本文报道Shh通过一条直接调节肌动蛋白细胞骨架的新途径调节海马锥体神经元树突棘的形成。Shh信号分子补丁(PTC)和平滑(Smo)在包括小脑Purkinje细胞和海马锥体神经元在内的几种有丝分裂后神经元中表达，Smo抑制Gli介导的转录活性Smo依赖地诱导培养的海马神经元树突棘的形成。Smo通过其胞浆C末端抑制Tiam1或rac1的活性而与Tiam1相互作用。SMO基因敲除Shh诱导小鼠胚胎成纤维细胞肌动蛋白细胞骨架重塑不依赖于转录激活。这些发现证明了一种新的Shh途径，它通过Tiam1-rac1激活(C)2010 Elsevier Inc.
The sonic hedgehog (Shh) pathway has essential roles in several processes during development of the vertebrate central nervous system (CNS) Here we report that Shh regulates dendrite spine formation in hippocampal pyramidal neurons via a novel pathway that directly regulates the actin cytoskeleton Shh signaling molecules Patched (Ptc) and Smoothened (Smo) are expressed in several types of postmitotic neurons including cerebellar Purkinje cells and hippocampal pyramidal neurons Knockdown of Smo induces dendrite spine formation in cultured hippocampal neurons Independently of Gli mediated transcriptional activity Smo interacts with Tiam1 a guanine nucleotide exchange factor for Rac1 via its cytoplasmic C-terminal region Inhibition of Tiam1 or Rac1 activity suppresses spine induction by Smo knockdown Shh Induces remodeling of the actin cytoskeleton independently of transcriptional activation in mouse embryonic fibroblasts These findings demonstrate a novel Shh pathway that regulates the actin eytoskeleton via Tiam1-Rac1 activation (C) 2010 Elsevier Inc All rights reserved