Targeting of PKA to Glutamate Receptors through a MAGUK-AKAP Complex

  title={Targeting of PKA to Glutamate Receptors through a MAGUK-AKAP Complex},
  author={Marcie Colledge and Rebecca A. Dean and Gregory Scott and Lorene K Langeberg and Richard L. Huganir and John D. Scott},

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Role of AKAP5 in p ostsynaptic signaling complexes
It is found that AKAP5 anchored PKA activity was required for full β2AR stimulation-induced GluA1 Ser845 phosphorylation, which mediate most excitatory synaptic transmission in mammalian CNS.
Regulation of GluR1 by the A-Kinase Anchoring Protein 79 (AKAP79) Signaling Complex Shares Properties with Long-Term Depression
It is demonstrated that AKAP79 not only promotes basal phosphorylation of Ser845 but also confers a calcium- and PP2B-mediated downregulation to GluR1 receptor currents, suggesting that the integration of intracellular signals relevant for LTD may be transduced to GLUR1 by theAKAP79 signaling complex.
Role for A Kinase-anchoring Proteins (AKAPS) in Glutamate Receptor Trafficking and Long Term Synaptic Depression*
It is shown that a threshold level of NMDA receptor activation must be exceeded to trigger a stable loss of AMPA receptors from the surface of cultured hippocampal neurons, and it is demonstrated in hippocampal slices that displacement of PKA from AKADs occludes synaptically induced long term depression.
AKAP79/150 Impacts Intrinsic Excitability of Hippocampal Neurons through Phospho-Regulation of A-type K+ Channel Trafficking
It is demonstrated that AKAP79/150 provides a platform for dynamic PKA regulation of Kv4.2 expression, fundamentally impacting CA1 excitability and disrupting PKA anchoring led to a decrease in neuronal excitability, while preventing dephosphorylation by the phosphatase calcineurin resulted in increased excitability.
A critical role for PSD-95/AKAP interactions in endocytosis of synaptic AMPA receptors
The results suggest that PSD-95's interaction with AKAP150 is critical for NMDAR-triggered AMPAR endocytosis and LTD, possibly because these scaffolds position calcineurin in the appropriate subsynaptic domain.
A GluR1-cGKII Interaction Regulates AMPA Receptor Trafficking
AKAP79 Selectively Enhances Protein Kinase C Regulation of GluR1 at a Ca2+-Calmodulin-dependent Protein Kinase II/Protein Kinase C Site*
  • S. J. Tavalin
  • Biology, Chemistry
    Journal of Biological Chemistry
  • 2008
Biochemical studies demonstrate that AKAP79 localizes PKC activity near the receptor, thus accelerating Ser-831 phosphorylation, and provides a mechanism to overcome limitations in kinase abundance thereby ensuring faithful signal propagation and efficient modification of AMPA receptor-mediated responses.


Regulation of NMDA receptors by an associated phosphatase-kinase signaling complex.
Yotiao is a scaffold protein that physically attaches PP1 and PKA to NMDA receptors to regulate channel activity and targeting of these enzymes near the substrate is proposed to enhance phosphorylation-dependent modulation.
Glutamate Receptor Anchoring Proteins and the Molecular Organization of Excitatory Synapses
  • M. Sheng, D. Pak
  • Biology, Chemistry
    Annals of the New York Academy of Sciences
  • 1999
The cytoplasmic C‐terminal tail of certain glutamate receptor subunits interact with specific PDZ domain‐containing proteins, which may underlie the clustering, targeting, and immobilization of the glutamate receptors at postsynaptic sites.
Anchoring of protein kinase A is required for modulation of AMPA/kainate receptors on hippocampal neurons
Intracellular per-fusion of cultured hippocampal neurons with peptides derived from the conserved kinase binding region of AKAPs prevented the protein kinase A-mediated regulation of AMPA/kainate currents as well as fast excitatory synaptic currents, providing the first evidence that anchoring of protein kinases A is crucial in the regulation of synaptic function.
Regulation of kainate receptors by cAMP-dependent protein kinase and phosphatases
Currents induced by activation of the AMPA-kainate receptor were potentiated by agents that specifically stimulate adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase A (PKA) activity or were supported by intracellular application of the catalytic subunit of PKA by itself or in combination with cAMP.
GRIP: a synaptic PDZ domain-containing protein that interacts with AMPA receptors
GRIP is a new member of the PDZ domain-containing protein family which has seven PDZ domains and no catalytic domain and appears to serve as an adapter protein that links AMPA receptors to other proteins and may be critical for the clustering of AMPA receptor at excitatory synapses in the brain.
Association of protein kinase A and protein phosphatase 2B with a common anchoring protein.
Results suggest that both PKA and CaN are targeted to subcellular sites by association with a common anchor protein and thereby regulate the phosphorylation state of key neuronal substrates.