Diacylglycerol kinase ε regulates seizure susceptibility and long-term potentiation through arachidonoylinositol lipid signaling

Elena B. Rodriguez De Turco, Wen Tang, Matthew K. Topham, Fumio Sakane, Victor L. Marcheselli, Chu Chen, Akinobu Taketomi, Stephen M. Prescott, Nicolas G. Bazan

Research output: Contribution to journalArticlepeer-review

158 Scopus citations

Abstract

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 DGKε gene that showed, when expressed in COS-7 cells, selectivity for 20:4-DAG. The significance of DGKε in synaptic function was investigated in mice with targeted disruption of the DGKε. DGKε-/- mice showed a higher resistance to eletroconvulsive shock with shorter tonic seizures and faster recovery than DGKε+/+ 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 DGKε contributes to modulate neuronal signaling pathways linked to synaptic activity, neuronal plasticity, and epileptogenesis.

Original languageEnglish (US)
Pages (from-to)4740-4745
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number8
DOIs
StatePublished - Apr 10 2001
Externally publishedYes

ASJC Scopus subject areas

  • General

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