ERK regulation of phosphodiesterase 4 enhances dopamine-stimulated AMPA receptor membrane insertion

• DOI: 10.1073/pnas.1311783110
• Publication Date: 2013-08-29T04:32:58Z
• Authors: Roy S. Song; Ben Massenburg; Wendy Wenderski; Vino Jayaraman; Lauren Thompson; Susana R. Neves
• Keywords: Neurons; Analysis of Variance; 0303 health sciences; MAP Kinase Signaling System; Dopamine; Blotting, Western; Cell Membrane; Cyclic AMP-Dependent Protein Kinases; Models, Biological; Cyclic Nucleotide Phosphodiesterases, Type 4; Rats; Rats, Sprague-Dawley; 03 medical and health sciences; Animals; Immunoprecipitation; Receptors, AMPA

Significance ERK activity contributes to AMPA-type glutamate receptor (AMPAR) membrane insertion, but until now, there was no clear understanding how this regulation could happen. We have identified the motif of ERK inhibiting PDE4 and controlling PKA output as a key step in the dopamine-induced membrane trafficking of GluA1. The significance of this regulatory motif is that it provides a point of integration for ERK activating signals to modulate neuronal excitability by tuning the trafficking of AMPAR.