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Nascent Proteome Remodeling following Homeostatic Scaling at Hippocampal Synapses

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Schanzenbächer,  Christoph
Department of Molecular Membrane Biology, Max Planck Institute of Biophysics, Max Planck Society;
Department of Synaptic Plasticity, Max Planck Institute for Brain Research, Frankfurt am Main, Max Planck Society;

Sambandan,  Sivakumar
Department of Synaptic Plasticity, Max Planck Institute for Brain Research, Frankfurt am Main, Max Planck Society;

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Langer,  Julian David
Department of Molecular Membrane Biology, Max Planck Institute of Biophysics, Max Planck Society;

Schuman,  Erin M.
Department of Synaptic Plasticity, Max Planck Institute for Brain Research, Frankfurt am Main, Max Planck Society;

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Citation

Schanzenbächer, C., Sambandan, S., Langer, J. D., & Schuman, E. M. (2016). Nascent Proteome Remodeling following Homeostatic Scaling at Hippocampal Synapses. Neuron, 92(2), 358-371. doi:10.1016/j.neuron.2016.09.058.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002D-1D25-8
Abstract
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 downscaling 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.