Pak1 is involved in dendrite initiation as a downstream effector of Rac1 in cortical neurons

Pak1 is involved in dendrite initiation as a downstream effector of Rac1 in cortical neurons
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DOI:
10.1006/mcne.2002.1144
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发表时间:
2002-08-01
影响因子:
3.5
通讯作者:
Mikoshiba, K
Mikoshiba, K
中科院分区:
医学3区
文献类型:
--
作者:
Hayashi, K;Ohshima, T;Mikoshiba, K

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神经元中的树突发育是神经系统中复杂神经元网络形成的基础之一,并且已经证明Rho家族GTP酶(包括Rac 1、Cdc 42和RhoA)参与树突形成。Rac 1和Cdc 42的效应子之一,p21激活激酶1(Pak 1),在大脑中是丰富的;然而,Pak 1在神经元中的功能仍然未知。为了阐明Pak 1在神经元中的作用,我们通过一种新的基因转移技术,使用子宫内电穿孔将突变体Pak 1导入未成熟的神经元。引入组成型活性(CA)-Pak 1导致树突数量增加,而引入显性负性(DN)-Pak 1导致树突数量减少,并且CA-Rac 1和DN-Pak 1的共表达也导致树突数量减少。这些结果表明,Pak 1调节树突的起始作为下游效应的Rac 1。
Dendrite development in neurons is one of the bases for the formation of a complex neuronal network in the nervous system, and involvement of the Rho family GTPases, including Rac1, Cdc42, and RhoA, in dendrite formation has been demonstrated. One of the effectors of Rac1 and Cdc42, p21-activated kinase 1 (Pak1), is abundant in the brain; however, the function of Pak1 in neurons remains unknown. In order to clarify the roles of Pak1 in neurons, we introduced mutant Pak1 into immature neurons by a novel gene transfer technique using in utero electroporation. Introduction of constitutive active (CA)-Pak1 led to increase the number of dendrites, whereas introduction of dominant negative (DN)-Pak1 caused a reduction, and coexpression of CA-Rac1 and DN-Pak1 also resulted in a reduction in the number of dendrites. These results suggest that Pak1 regulates dendrite initiation as a downstream effector of Rac1.