Regulation of hippocampal long-term potentiation by p21-activated protein kinase 1 (PAK1)
Regulation of hippocampal long-term potentiation by p21-activated protein kinase 1 (PAK1)
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DOI：
10.1016/j.neuropharm.2008.06.055
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发表时间：
2009-01-01
影响因子：
4.7
通讯作者：
Jia, Zhengping
中科院分区：
文献类型：
--
作者：
Asrar, Suhail;Meng, Yanghong;Jia, Zhengping
Rho 家族小 GTP 酶在脊柱和突触特性的调节中发挥着重要作用，但其潜在机制尚不清楚。我们采用遗传方法创建并分析了蛋白激酶 PAKI 表达缺陷的敲除小鼠，该蛋白激酶 PAKI 与 Rho GTPases 直接相关并由 Rho GTPases 激活。我们证明，虽然这些基因敲除小鼠的基础功能和突触前功能均正常，但它们的海马 CA1 突触的长时程增强 (LTP) 选择性受损。与电生理缺陷一致，PAKI 基因敲除小鼠的肌动蛋白细胞骨架和肌动蛋白结合蛋白丝切蛋白出现变化。这些结果表明，PAK1 通过调节丝切蛋白活性和肌动蛋白细胞骨架，对海马突触可塑性至关重要。 (C) 2008 Elsevier Ltd. 保留所有权利。
The Rho family small GTPases are critically involved in the regulation of spine and synaptic properties, but the underlying mechanisms are poorly defined. We took genetic approaches to create and analyze knockout mice deficient in the expression of the protein kinase PAKI that is directly associated with and activated by the Rho GTPases. We demonstrated that while these knockout mice were normal in both basal and presynaptic function, they were selectively impaired in long-term potentiation (LTP) at hippocampal CA1 synapses. Consistent with the electrophysiological deficits, the PAKI knockout mice showed changes in the actin cytoskeleton and the actin binding protein cofilin. These results indicate that PAK1 is critical in hippocampal synaptic plasticity via regulating cofilin activity and the actin cytoskeleton. (C) 2008 Elsevier Ltd. All rights reserved.