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Dominant role of the GluR2 subunit in regulation of AMPA receptors by CaMKII

Abstract

GluR1 and GluR2 subunits compose AMPA receptors (AMPARs) in the mature hippocampus, and both the GluR1 subunit and Ca2+/calmodulin-dependent protein kinase II (CaMKII) are required for synaptic plasticity, memory and learning. Although GluR1 phosphorylation by CaMKII is preserved, the functional regulation of AMPARs by phosphorylation is lost in the presence of the GluR2 subunit. Our findings define a previously unknown, dominant role of the GluR2 subunit in signaling mediated by CaMKII at AMPARs.

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Figure 1: GluR2 subunit eliminated the regulation of GluR1/GluR2 heteromers by CaMKII.
Figure 2: The GluR2 subunit did not affect CaMKII phosphorylation of Ser831 in hippocampal AMPARs during synaptic potentiation.
Figure 3: GluR2 subunit preserves GluR1/GluR2 heteromers in a low-conductance state, regardless of Ser831 phosphorylation.

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Acknowledgements

We thank P. Stork, L. Trussell, C. Jahr and T. Soderling for helpful suggestions. Supported by US National Institutes of Health grants NS47773 (M.C.O.) and NS27037 (T. Soderling and V.A.D.) and a Medical Research Foundation grant (V.A.D.).

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Correspondence to Victor A Derkach.

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Supplementary information

Supplementary Fig. 1

GISP evoked a long-lasting potentiation of AMPAR mEPSCs in cultured hippocampal neurons. (PDF 518 kb)

Supplementary Fig. 2

Constitutively active CaMKII phosphorylated GluR1 Ser831 similarly in GluR1 homomers and GluR1/GluR2 heteromers expressed in HEK293 cells. (PDF 800 kb)

Supplementary Fig. 3

Properties of GluR1/GluR2 heteromers were very different from either GluR1 or GluR2 homomers. (PDF 775 kb)

Supplementary Table 1

GluR2 subunit blocks the regulation of single-channel conductance (γ) of GluR1/GluR2 heteromers by CaMKII or Ser831 to Asp mutation. (PDF 60 kb)

Supplementary Methods (PDF 275 kb)

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Oh, M., Derkach, V. Dominant role of the GluR2 subunit in regulation of AMPA receptors by CaMKII. Nat Neurosci 8, 853–854 (2005). https://doi.org/10.1038/nn1476

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