NMDA receptor-mediated control of protein synthesis at developing synapses

Abstract

We demonstrate a rapid and complex effect of N-methyl-d-aspartate receptor (NMDAR) activation on synaptic protein synthesis in the superior colliculi of young rats. Within minutes of receptor activation, translation of alpha Ca2+/calmodulin dependent kinase II (αCamK II) was increased, whereas total protein synthesis was reduced. NMDAR activation also increased phosphorylation of eukaryotic elongation factor 2 (eEF2), a process known to inhibit protein translation by reducing peptide chain elongation. Low doses of cycloheximide, which reduce elongation rate independently of eEF2 phosphorylation, decreased overall protein synthesis but increased αCaMK II synthesis. These observations suggest that regulation of peptide elongation via eEF2 phosphorylation can link NMDAR activation to local increases in the synthesis of specific proteins during activity-dependent synaptic change.

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Figure 1: NMDAR activation dynamically regulates protein synthesis in synaptic preparations.
Figure 2: Alpha CaMK II synthesis is increased by NMDAR activation.
Figure 3: Inhibition of synaptic translation elongation.

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Acknowledgements

This work was supported by U.S. Public Health Service Grants EY 06039 to M.C.P and GM 50402 to A.C.N.

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Correspondence to A. J. Scheetz.

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Scheetz, A., Nairn, A. & Constantine-Paton, M. NMDA receptor-mediated control of protein synthesis at developing synapses. Nat Neurosci 3, 211–216 (2000). https://doi.org/10.1038/72915

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