TY - JOUR
T1 - Diacylglycerol kinase ε regulates seizure susceptibility and long-term potentiation through arachidonoylinositol lipid signaling
AU - Rodriguez De Turco, Elena B.
AU - Tang, Wen
AU - Topham, Matthew K.
AU - Sakane, Fumio
AU - Marcheselli, Victor L.
AU - Chen, Chu
AU - Taketomi, Akinobu
AU - Prescott, Stephen M.
AU - Bazan, Nicolas G.
PY - 2001/4/10
Y1 - 2001/4/10
N2 - 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.
AB - 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.
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U2 - 10.1073/pnas.081536298
DO - 10.1073/pnas.081536298
M3 - Article
C2 - 11287665
AN - SCOPUS:0035836345
SN - 0027-8424
VL - 98
SP - 4740
EP - 4745
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 8
ER -