Mechanism of Ca2+/calmodulin-dependent kinase II regulation of AMPA receptor gating
Open Access
- 24 April 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Neuroscience
- Vol. 14 (6), 727-735
- https://doi.org/10.1038/nn.2804
Abstract
CaMKII phosphorylates the GluA1 AMPA subunit at Ser831 to increase single channel conductance. Here, the authors show that coexpression of TARPs is required for phospho-Ser831 to increase conductance of GluA1/GluA2 receptors. Ser831 phosphorylation increases the efficiency with which each subunit can activate, increasing the likelihood of simultaneous subunit activation during gating. The function, trafficking and synaptic signaling of AMPA receptors are tightly regulated by phosphorylation. Ca2+/calmodulin-dependent kinase II (CaMKII) phosphorylates the GluA1 AMPA receptor subunit at Ser831 to increase single-channel conductance. We show that CaMKII increases the conductance of native heteromeric AMPA receptors in mouse hippocampal neurons through phosphorylation of Ser831. In addition, co-expression of transmembrane AMPA receptor regulatory proteins (TARPs) with recombinant receptors is required for phospho-Ser831 to increase conductance of heteromeric GluA1-GluA2 receptors. Finally, phosphorylation of Ser831 increases the efficiency with which each subunit can activate, independent of agonist efficacy, thereby increasing the likelihood that more receptor subunits will be simultaneously activated during gating. This underlies the observation that phospho-Ser831 increases the frequency of openings to larger conductances rather than altering unitary conductance. Together, these findings suggest that CaMKII phosphorylation of GluA1-Ser831 decreases the activation energy for an intrasubunit conformational change that regulates the conductance of the receptor when the channel pore opens.Keywords
This publication has 51 references indexed in Scilit:
- Characterizing Single-Channel Behavior of GluA3 ReceptorsBiophysical Journal, 2010
- X-ray structure, symmetry and mechanism of an AMPA-subtype glutamate receptorNature, 2009
- TARP modulation of synaptic AMPA receptor trafficking and gating depends on multiple intracellular domainsProceedings of the National Academy of Sciences of the United States of America, 2009
- Regulation of AMPA receptor extrasynaptic insertion by 4.1N, phosphorylation and palmitoylationNature Neuroscience, 2009
- AKAP79 Selectively Enhances Protein Kinase C Regulation of GluR1 at a Ca2+-Calmodulin-dependent Protein Kinase II/Protein Kinase C SitePublished by Elsevier BV ,2008
- A GluR1-cGKII Interaction Regulates AMPA Receptor TraffickingNeuron, 2007
- NMDA receptor‐dependent long‐term potentiation in mouse hippocampal interneurons shows a unique dependence on Ca2+/calmodulin‐dependent kinasesThe Journal of Physiology, 2007
- Identification and characterization of a novel phosphorylation site on the GluR1 subunit of AMPA receptorsMolecular and Cellular Neuroscience, 2007
- TARP Subtypes Differentially and Dose-Dependently Control Synaptic AMPA Receptor GatingNeuron, 2007
- Stargazin attenuates intracellular polyamine block of calcium-permeable AMPA receptorsNature Neuroscience, 2007