ERK activation causes epilepsy by stimulating NMDA receptor activity
作者： Abdolrahman S Nateri , Gennadij Raivich , Christine Gebhardt , Clive Da Costa , Heike Naumann
关键词:
摘要: The ERK MAPK signalling pathway is a highly conserved kinase cascade linking transmembrane receptors to downstream effector mechanisms. To investigate the function of in neurons, constitutively active form MEK1 (caMEK1) was conditionally expressed murine brain, which resulted activation and caused spontaneous epileptic seizures. stimulated phosphorylation eukaryotic translation initiation factor 4E (eIF4E) augmented NMDA receptor 2B (NR2B) protein levels. Pharmacological inhibition NR2B impaired synaptic facilitation area cornus ammonicus region 3 (CA3) acute hippocampal slices derived from caMEK1-expressing mice abrogated epilepsy vivo. In addition, expression caMEK1 transcription factor, cAMP response element-binding (CREB) increased ephrinB2. EphrinB2 overexpression tyrosine phosphorylation, essential for caMEK1-induced vivo, since conditional inactivation ephrinB2 greatly reduced seizure frequency transgenic mice. Therefore, our study identifies mechanism epileptogenesis that links MAP Eph/Ephrin signalling.
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