Rodriguez de Turco E B, Tang W, Topham M K, Sakane F, Marcheselli V L, Chen C, Taketomi A, Prescott S M, Bazan N G
Neuroscience Center of Excellence and Department of Ophthalmology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4740-5. doi: 10.1073/pnas.081536298. Epub 2001 Apr 3.
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 DGKepsilon gene that showed, when expressed in COS-7 cells, selectivity for 20:4-DAG. The significance of DGKepsilon in synaptic function was investigated in mice with targeted disruption of the DGKepsilon. DGKepsilon(-/-) mice showed a higher resistance to electroconvulsive shock with shorter tonic seizures and faster recovery than DGKepsilon(+/+) 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 DGKepsilon contributes to modulate neuronal signaling pathways linked to synaptic activity, neuronal plasticity, and epileptogenesis.
花生四烯酸二酰基甘油（20:4-DAG）是一种第二信使，它由磷脂酰肌醇4,5-二磷酸衍生而来，通过与G蛋白偶联的谷氨酸代谢型受体的刺激和磷脂酶C的激活而产生。20:4-DAG信号通过二酰基甘油激酶（DGK）催化其磷酸化为磷脂酸而终止。我们克隆了小鼠DGKepsilon基因，该基因在COS-7细胞中表达时，对20:4-DAG具有选择性。通过对DGKepsilon进行靶向破坏的小鼠来研究DGKepsilon在突触功能中的意义。与DGKepsilon(+/+)小鼠相比，DGKepsilon(-/-)小鼠对电惊厥休克具有更高的抵抗力，强直性惊厥持续时间更短，恢复更快。大脑皮质中的磷脂酰肌醇4,5-二磷酸信号通路受到极大影响，导致20:4-DAG和游离20:4的积累减少。此外，穿通通路-齿状颗粒细胞突触中的长时程增强作用减弱。我们提出，DGKepsilon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。
