Specific roles of Akt iso forms in apoptosis and axon growth regulation in neurons.
Specific roles of Akt iso forms in apoptosis and axon growth regulation in neurons.
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DOI：
10.1371/journal.pone.0032715
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wandosell F
中科院分区：
文献类型：
--
作者：
Diez H;Garrido JJ;Wandosell F
AKT是AGC激酶家族的一员，由三种亚型组成。作为I类PI3激酶途径的主要调节者之一，它在控制细胞代谢、生长和存活方面起着关键作用。尽管它在神经系统中得到了广泛的研究，但我们对每种异构体在分化神经元中的具体作用知之甚少。在这里，我们使用大脑皮层和海马神经元培养来分析它们的功能。我们用一种特殊的shRNA方法研究了Akt异构体及其底物在神经元发育不同阶段的表达和功能，以阐明每种异构体在神经元存活、轴突发育和细胞信号传递中的作用。我们的结果表明，三种Akt亚型在许多过程中都显示出实质性的补偿作用。然而，Akt2和AKT3的破坏显著降低了神经元的存活率和轴突长度。这些变化与caspase3活性增加和mTORC1途径某些元件的磷酸化减少有关。事实上，Akt2的减少和AKT3的抑制更明显地减少了S6的表达和磷酸化。所有这些数据表明，Akt2和AKT3特异性地调控培养神经元的某些方面的凋亡和细胞生长，并可能有助于理解神经元死亡的机制和表现为放松调控的生长的病理。
Akt is a member of the AGC kinase family and consists of three isoforms. As one of the major regulators of the class I PI3 kinase pathway, it has a key role in the control of cell metabolism, growth, and survival. Although it has been extensively studied in the nervous system, we have only a faint knowledge of the specific role of each isoform in differentiated neurons. Here, we have used both cortical and hippocampal neuronal cultures to analyse their function. We characterized the expression and function of Akt isoforms, and some of their substrates along different stages of neuronal development using a specific shRNA approach to elucidate the involvement of each isoform in neuron viability, axon development, and cell signalling. Our results suggest that three Akt isoforms show substantial compensation in many processes. However, the disruption of Akt2 and Akt3 significantly reduced neuron viability and axon length. These changes correlated with a tendency to increase in active caspase 3 and a decrease in the phosphorylation of some elements of the mTORC1 pathway. Indeed, the decrease of Akt2 and more evident the inhibition of Akt3 reduced the expression and phosphorylation of S6. All these data indicate that Akt2 and Akt3 specifically regulate some aspects of apoptosis and cell growth in cultured neurons and may contribute to the understanding of mechanisms of neuron death and pathologies that show deregulated growth.
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影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
10.5
作者：
Chalhoub, Nader;Zhu, Guo;Baker, Suzanne J.
通讯作者：
Baker, Suzanne J.
影响因子：
30.8
作者：
Emamian, ES;Hall, D;Gogos, JA
通讯作者：
Gogos, JA
DOI：
10.1016/s0960-0760(02)00261-3
发表时间：
2002-12-01
影响因子：
4.1
作者：
Cardona-Gómez, GP;Mendez, P;Garcia-Segura, LM
通讯作者：
Garcia-Segura, LM
影响因子：
11.2
作者：
Endersby R;Zhu X;Hay N;Ellison DW;Baker SJ
通讯作者：
Baker SJ