Postsynaptic decoding of neural activity: eEF2 as a biochemical sensor coupling miniature synaptic transmission to local protein synthesis.
Activity-dependent regulation of dendritic protein synthesis is critical for enduring changes in synaptic function, but how the unique features of distinct activity patterns are decoded by the dendritic translation machinery remains poorly understood. Here, we identify eukaryotic elongation factor-2 (eEF2), which catalyzes ribosomal translocation during protein synthesis, as a biochemical sensor in dendrites that is specifically and locally tuned to the quality of neurotransmission. We show that intrinsic action potential (AP)-mediated network activity in cultured hippocampal neurons maintains eEF2 in a relatively dephosphorylated (active) state, whereas spontaneous neurotransmitter release (i.e., miniature neurotransmission) strongly promotes the phosphorylation (and inactivation) of eEF2. The regulation of eEF2 phosphorylation is responsive to bidirectional changes in miniature neurotransmission and is controlled locally in dendrites. Finally, direct spatially controlled inhibition of eEF2 phosphorylation induces local translational activation, suggesting that eEF2 is a biochemical sensor that couples miniature synaptic events to local translational suppression in neuronal dendrites.
Sutton
Michael A
MA
Division of Biology 114-96, California Institute of Technology, Pasadena, CA 91125, USA.
Taylor
Anne M
AM
Ito
Hiroshi T
HT
Pham
Anh
A
Schuman
Erin M
EM
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D003712:Dendrites / Q000502:physiology*; D003952:Diagnostic Imaging; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D014176:Protein Biosynthesis; D051381:Rats; D009435:Synaptic Transmission / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014162:Transfection / Q000379:methods
D015852:Eukaryotic Initiation Factor-2; D018691:Excitatory Amino Acid Antagonists; D049452:Green Fluorescent Proteins; D013779:Tetrodotoxin