Localized activation of p21-activated kinase controls neuronal polarity and morphology.
Localized activation of p21-activated kinase controls neuronal polarity and morphology.
复制标题
p21激活激酶的局部激活控制神经元的极性和形态。
DOI：
10.1523/jneurosci.0765-07.2007
复制
发表时间：
2007-08-08
影响因子：
5.3
通讯作者：
Nikolic, Margareta
中科院分区：
文献类型：
--
作者：
Jacobs, Tom;Causeret, Frederic;Nishimura, Yoshiaki V;Terao, Mami;Norman, Adele;Hoshino, Mikio;Nikolic, Margareta
在发育中的前脑，神经元极化是一个逐步的、最初可逆的过程，是正确迁移和轴突指定的基础。伴随极化而来的细胞骨架变化的许多方面目前在分子上是不确定的，因此人们对此知之甚少。在这里，我们揭示了Ak1激酶对于轴突和树突的指定是必不可少的。在海马神经元中，PAK1的激活在空间上仅限于未成熟轴突，尽管它均匀地存在于所有轴突中。在所有神经突起的膜上，pak1的过度激活或pak1表达的丧失都会破坏神经元的形态以及轴突和树突之间的区别。我们发现Ak1以一种依赖于激酶的方式作用于极性，至少部分地通过rac1和cofilin影响F-肌动蛋白和微管细胞骨架。我们的数据首次证明了定位的蛋白激酶1激活对神经元极化和分化的重要性。
In the developing forebrain neuronal polarisation is a stepwise and initially reversible process that underlies correct migration and axon specification. Many aspects of cytoskeletal changes that accompany polarisation are currently molecularly undefined and thus poorly understood. Here we reveal that the Pak1 kinase is essential for the specification of an axon and dendrites. In hippocampal neurones activation of Pak1 is spatially restricted to the immature axon despite its uniform presence in all neurites. Hyperactivation of Pak1 at the membrane of all neurites or loss of Pak1 expression disrupt both neuronal morphology and the distinction between an axon and dendrites. We reveal that Pak1 acts on polarity in a kinase dependent manner, by affecting the F-actin and microtubule cytoskeleton at least in part through Rac1 and cofilin. Our data are the first to demonstrate the importance of localised Pak1 kinase activation for neuronal polarisation and differentiation.