D1 Dopamine Receptor Activation Induces Neuronal eEF2 Pathway-Dependent Protein Synthesis.

ABSTRACT: Dopamine, alongside other neuromodulators, defines brain and neuronal states, inter alia through regulation of global and local mRNA translation. Yet, the signaling pathways underlying the effects of dopamine on mRNA translation and psychiatric disorders are not clear. In order to examine the molecular pathways downstream of dopamine receptors, we used genetic, pharmacologic, biochemical, and imaging methods, and found that activation of dopamine receptor D1 but not D2 leads to rapid dephosphorylation of eEF2 at Thr⁵⁶ but not eIF2α in cortical primary neuronal culture in a time-dependent manner. NMDA receptor, mTOR, and ERK pathways are upstream of the D1 receptor-dependent eEF2 dephosphorylation and essential for it. Furthermore, D1 receptor activation resulted in a majo

SUBMITTER: David O 

PROVIDER: S-EPMC7242790 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature