Diacylglycerol kinase ɛ regulates seizure susceptibility and long-term potentiation through arachidonoyl– inositol lipid signaling

Diacylglycerol kinase ɛ regulates seizure susceptibility and long-term potentiation through arachidonoyl– inositol lipid signaling
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二酰甘油激酶 ɛ 通过花生四烯酰肌醇脂质信号传导调节癫痫易感性和长期增强

DOI:
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发表时间:
2001
影响因子:
11.1
通讯作者:
N. Bazan
N. Bazan
中科院分区:
综合性期刊1区
文献类型:
--
作者:
E. B. Rodriguez de Turco;W. Tang;M. Topham;F. Sakane;V. Marcheselli;Chu Chen;A. Taketomi;S. Prescott;N. Bazan

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花生四烯酸二酰甘油(20:4-DAG)是一种第二信使,来源于磷脂酰肌醇4,5-二磷酸,通过刺激与G蛋白连接的谷氨酸代谢型受体和激活磷脂酶C产生。20:4-DAG信号传导通过其磷酸化为磷脂酸而终止,由二酰基甘油激酶(DGK)催化。我们已经克隆了鼠DGK β基因,当在COS-7细胞中表达时,该基因显示出对20:4-DAG的选择性。在具有DGK β靶向破坏的小鼠中研究了DGK β在突触功能中的意义。与DGK <$+/+小鼠相比,DGK <$−/−小鼠对电休克表现出更高的抵抗力,强直性发作时间更短,恢复更快。大脑皮层中的磷脂酰肌醇4,5-二磷酸信号传导途径受到极大影响,导致20:4-DAG和游离20:4的积累降低。此外,长时程增强衰减在穿孔路径齿状颗粒细胞突触。我们认为,DGK α有助于调节与突触活动、神经元可塑性和癫痫发生相关的神经元信号通路。
Arachidonoyldiacylglycerol (20:4-DAG) is a second messenger derived from phosphatidylinositol 4,5-bisphosphate and generated by stimulation of glutamate metabotropic receptors linked to G proteins and activation of phospholipase C. 20:4-DAG signaling is terminated by its phosphorylation to phosphatidic acid, catalyzed by diacylglycerol kinase (DGK). We have cloned the murine DGKɛ gene that showed, when expressed in COS-7 cells, selectivity for 20:4-DAG. The significance of DGKɛ in synaptic function was investigated in mice with targeted disruption of the DGKɛ. DGKɛ−/− mice showed a higher resistance to eletroconvulsive shock with shorter tonic seizures and faster recovery than DGKɛ+/+ mice. The phosphatidylinositol 4,5-bisphosphate-signaling pathway in cerebral cortex was greatly affected, leading to lower accumulation of 20:4-DAG and free 20:4. Also, long-term potentiation was attenuated in perforant path–dentate granular cell synapses. We propose that DGKɛ contributes to modulate neuronal signaling pathways linked to synaptic activity, neuronal plasticity, and epileptogenesis.
DOI: 10.1152/jn.2001.85.1.384
发表时间: 2001-01-01
影响因子: 2.5
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通讯作者: Bazan, NG
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