Ebr. De Turco et al., Diacylglycerol kinase epsilon regulates seizure susceptibility and long-term potentiation through arachidonoylinositol lipid signaling, P NAS US, 98(8), 2001, pp. 4740-4745
Citations number
37
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Arachidonoyldiacylglycerol (20:4-DAG) is a second messenger derived from ph
osphatidylinositol 4,5-bisphosphate and generated by stimulation of glutama
te metabotropic receptors linked to C proteins and activation of phospholip
ase C. 20:4-DAG signaling is terminated by its phosphorylation to phosphati
dic acid, catalyzed by diacylglycerol kinase (DGK). We have cloned the muri
ne DGK epsilon gene that showed, when expressed in COS-7 cells, selectivity
for 20:4-DAG. The significance of DGKe in synaptic function was investigat
ed in mice with targeted disruption of the DGK epsilon. DCK epsilon (-/-) m
ice showed a higher resistance to eletroconvulsive shock with shorter tonic
seizures and faster recovery than DGK epsilon (+/+) mice. The phosphatidyl
inositol 4,5-bisphosphate-signaling pathway in cerebral cortex was greatly
affected, leading to lower accumulation of 20:4-DAG and free 20:4. Also, lo
ng-term potentiation was attenuated in perforant path-dentate granular cell
synapses. We propose that DGK epsilon contributes to modulate neuronal sig
naling pathways linked to synaptic activity, neuronal plasticity, and epile
ptogenesis.