Regulation of GluR1 by the A-kinase anchoring protein 79 (AKAP79) signaling complex shares properties with long-term depression

Steven J. Tavalin, Marcie Colledge, Johannes W Hell, Lorene K. Langeberg, Richard L. Huganir, John D. Scott

Research output: Contribution to journalArticle

186 Scopus citations

Abstract

Second messengers regulate synaptic plasticity by influencing the balance between kinase and phosphatase activity. One target of this balance is the phosphorylation state of the AMPA receptor glutamate receptor 1 (GluR1) subunit. Hippocampal long-term depression (LTD) is a calcium-dependent downregulation of synaptic AMPA receptor currents associated with dephosphorylation of Ser845, a cAMP-dependent protein kinase (PKA) site on GluR1. Recruitment of kinases and phosphatases to the AMPA receptor might enable modulation of AMPA receptor function. The neuronal A-kinase anchoring protein AKAP79/150 interacts with PKA and the calcium-dependent protein phosphatase PP2B and is linked to the AMPA receptor GluR1 subunit by synapse-associated protein 97 (SAP97), a membrane-associated guanylate kinase family protein. Here we demonstrate that AKAP79 not only promotes basal phosphorylation of Ser845 but also confers a calcium- and PP2B-mediated downregulation to GluR1 receptor currents. This AKAP79-dependent downregulation is contingent on the local presence of PKA, Ser845 of GluR1, and a PDZ (postsynaptic density 95/Discs large/zona occludens 1)-domain interaction between GluR1 and SAP97, all of which support basal phosphorylation of the receptor. These findings suggest that the AKAP79 signaling complex is sufficient to couple intracellular calcium levels to the PKA phosphorylation state of GluR1. Thus, the integration of intracellular signals relevant for LTD may be transduced to GluR1 by the AKAP79 signaling complex.

Original languageEnglish (US)
Pages (from-to)3044-3051
Number of pages8
JournalJournal of Neuroscience
Volume22
Issue number8
StatePublished - Apr 15 2002
Externally publishedYes

Keywords

  • AKAP79
  • AMPA receptor
  • Calcium
  • cAMP
  • Kinase
  • Phosphatase
  • Synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Tavalin, S. J., Colledge, M., Hell, J. W., Langeberg, L. K., Huganir, R. L., & Scott, J. D. (2002). Regulation of GluR1 by the A-kinase anchoring protein 79 (AKAP79) signaling complex shares properties with long-term depression. Journal of Neuroscience, 22(8), 3044-3051.