期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 98, 期 8, 页码 4740-4745出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.081536298
关键词
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资金
- NCI NIH HHS [P30 CA042014, CA59548, CA42014] Funding Source: Medline
- NINDS NIH HHS [R01 NS023002, R01-NS-23002] Funding Source: Medline
Arachidonoyldiacylglycerol (20:4-DAG) is a second messenger derived from phosphatidylinositol 4,5-bisphosphate and generated by stimulation of glutamate metabotropic receptors linked to C 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 DGK epsilon gene that showed, when expressed in COS-7 cells, selectivity for 20:4-DAG. The significance of DGKe in synaptic function was investigated in mice with targeted disruption of the DGK epsilon. DCK epsilon (-/-) mice showed a higher resistance to eletroconvulsive shock with shorter tonic seizures and faster recovery than DGK epsilon (+/+) 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 DGK epsilon contributes to modulate neuronal signaling pathways linked to synaptic activity, neuronal plasticity, and epileptogenesis.
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