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NMDA receptor-mediated control of protein synthesis at developing synapses

Nature Neurosciencevolume 3pages211216 (2000) | Download Citation

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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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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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Author notes

    • Martha Constantine-Paton

    Present address: Department of Biology, Massachusetts Institute of Technology, Building 68, Rm 380, 77 Massachusetts Ave., Cambridge, Massachusetts, 02139-4307, USA

    • A. J. Scheetz

    Present address: Department of Molecular Biophysics & Biochemistry, Yale University, 333 Cedar St., P.O. Box 208024, New Haven, Connecticut, 06520-8024, USA

Affiliations

  1. Department of Molecular, Cellular and Developmental Biology, Yale University, Kline Biology Tower, P.O. Box 208103, New Haven, 06520-8103, Connecticut, USA

    • A. J. Scheetz
    •  & Martha Constantine-Paton
  2. Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, Box 296, 1230 York Avenue, New York, 10021, New York, USA

    • Angus C. Nairn

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Correspondence to A. J. Scheetz.

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https://doi.org/10.1038/72915

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