Phosphoinositide 3-kinase enhancer regulates neuronal dendritogenesis and survival in neocortex.
Phosphoinositide 3-kinase enhancer regulates neuronal dendritogenesis and survival in neocortex.
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DOI：
10.1523/jneurosci.1129-11.2011
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发表时间：
2011-06-01
期刊：
影响因子：
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通讯作者：
Ye K
中科院分区：
文献类型：
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作者：
Chan CB;Liu X;Pradoldej S;Hao C;An J;Yepes M;Luo HR;Ye K
磷脂酰肌醇3-激酶增强子(Pike)结合并增强PI3K/Akt活性。然而，它在大脑中的生理功能却从未被研究过。在这里，我们表明Pike在调节新皮质神经元的存活和发育中起着重要的作用。在发育过程中，在Pike基因敲除(Pike−/−)皮层的脑室区域观察到细胞凋亡增强。此外，Pike−/−神经元表现出树突复杂性、树突分支长度和胞体大小的降低。这些缺陷是由于Pike−/−神经元中PI3K/Akt活性降低所致，因为在体外或在Pike−/−PTEN−/−双基因敲除小鼠中，PI3K/Akt级联通路的增强可以挽救受损的树突分支。有趣的是，派克−/−小鼠在运动和空间导航方面表现出行为异常。由于PI3K/AKT活性降低，Pike−/−神经元更容易受到谷氨酸或中风诱导的神经细胞死亡的影响。总之，我们的数据证实了Pike通过证实PI3K/Akt通路在调节神经元生存和发育中的关键作用。
Phosphoinositide 3-kinase enhancer (PIKE) binds and enhances PI3K/Akt activities. However, its physiological functions in brain have never been explored. Here we show that PIKE is important in regulating the neuronal survival and development of neocortex. During development, enhanced apoptosis is observed in the ventricular zone of PIKE knockout (PIKE −/−) cortex. Moreover, PIKE −/− neurons show reduced dendritic complexity, dendritic branch length and soma size. These defects are due to the reduced PI3K/Akt activities in PIKE −/− neurons, as the impaired dendritic arborization can be rescued when PI3K/Akt cascade is augmented in vitro or in PIKE−/−PTEN−/− double knockout mice. Interestingly, PIKE −/− mice display behavioral abnormality in locomotion and spatial navigation. Because of the diminished PI3K/Akt activities, PIKE −/− neurons are more vulnerable to glutamate or stroke-induced neuronal cell death. Together, our data established the critical role of PIKE in regulating neuronal survival and development by substantiating the PI3K/Akt pathway.