PKA phosphorylation of AMPA receptor subunits controls synaptic trafficking underlying plasticity

José A. Esteban, Song Hai Shi, Christopher Wilson, Mutsuo Nuriya, Richard L. Huganir, Roberto Malinow

Research output: Contribution to journalArticle

596 Citations (Scopus)


The regulated incorporation of AMPA receptors into synapses is important for synaptic plasticity. Here we examine the role of protein kinase A (PKA) in this process. We found that PKA phosphorylation of the AMPA receptor subunits GluR4 and GluR1 directly controlled the synaptic incorporation of AMPA receptors in organotypic slices from rat hippocampus. Activity-driven PKA phosphorylation of GluR4 was necessary and sufficient to relieve a retention interaction and drive receptors into synapses. In contrast, PKA phosphorylation of GluR1 and the activity of calcium/calmodulin-dependent kinase II (CaMKII) were both necessary for receptor incorporation. Thus, PKA phosphorylation of AMPA receptor subunits contributes to diverse mechanisms underlying synaptic plasticity.

Original languageEnglish
Pages (from-to)136-143
Number of pages8
JournalNature Neuroscience
Issue number2
Publication statusPublished - 2003 Feb 1


ASJC Scopus subject areas

  • Neuroscience(all)

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