NMDA receptor-mediated control of protein synthesis at developing synapses.
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 (alphaCamK 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 alphaCaMK 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.
Scheetz
A J
AJ
Department of Molecular, Cellular and Developmental Biology, Yale University, Kline Biology Tower, P.O. Box 208103, New Haven, Connecticut 06520-8103, USA. alfred.scheetz@yale.edu
Nairn
A C
AC
Constantine-Paton
M
M
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D015180:Electrophoresis, Gel, Two-Dimensional; D018698:Glutamic Acid / Q000494:pharmacology; D007526:Isoelectric Point; D008970:Molecular Weight; D016202:N-Methylaspartate / Q000494:pharmacology; D020652:Peptide Elongation Factor 2 / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011233:Precipitin Tests; D014176:Protein Biosynthesis / Q000187:drug effects; D011506:Proteins / Q000737:chemistry; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000166:cytology; D013477:Superior Colliculi / Q000166:cytology* / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D013997:Time Factors
D020652:Peptide Elongation Factor 2; D011506:Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D003513:Cycloheximide; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases