Neuron
Volume 92, Issue 2, 19 October 2016, Pages 358-371
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Nascent Proteome Remodeling following Homeostatic Scaling at Hippocampal Synapses

https://doi.org/10.1016/j.neuron.2016.09.058Get rights and content
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Highlights

  • Newly synthesized proteins were metabolically labeled during homeostatic scaling

  • Approximately 6,000 newly synthesized proteins were detected using mass spectrometry

  • Over 300 proteins were differentially regulated by synaptic up- and down-scaling

  • Important synaptic proteins and disease-related proteins were regulated

Summary

Homeostatic scaling adjusts the strength of synaptic connections up or down in response to large changes in input. To identify the landscape of proteomic changes that contribute to opposing forms of homeostatic plasticity, we examined the plasticity-induced changes in the newly synthesized proteome. Cultured rat hippocampal neurons underwent homeostatic up-scaling or down-scaling. We used BONCAT (bio-orthogonal non-canonical amino acid tagging) to metabolically label, capture, and identify newly synthesized proteins, detecting and analyzing 5,940 newly synthesized proteins using mass spectrometry and label-free quantitation. Neither up- nor down-scaling produced changes in the number of different proteins translated. Rather, up- and down-scaling elicited opposing translational regulation of several molecular pathways, producing targeted adjustments in the proteome. We discovered ∼300 differentially regulated proteins involved in neurite outgrowth, axon guidance, filopodia assembly, excitatory synapses, and glutamate receptor complexes. We also identified differentially regulated proteins that are associated with multiple diseases, including schizophrenia, epilepsy, and Parkinson’s disease.

Keywords

proteomics
homeostatic scaling
transcriptomics
protein synthesis
synaptic plasticity
BONCAT

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