title: Nascent Proteome Remodeling following Homeostatic Scaling at Hippocampal Synapses.
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 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.
authors.affiliation: Max Planck Institute for Brain Research, Max von Laue Strasse 4, 60438 Frankfurt am Main, Germany; Max Planck Institute for Biophysics, Max von Laue Strasse 3, 60438 Frankfurt am Main, Germany.
authors.forename: Christoph T
authors.initials: CT
authors.lastname: Schanzenbächer
authors.affiliation: Max Planck Institute for Brain Research, Max von Laue Strasse 4, 60438 Frankfurt am Main, Germany.
authors.forename: Sivakumar
authors.initials: S
authors.lastname: Sambandan
authors.affiliation: Max Planck Institute for Brain Research, Max von Laue Strasse 4, 60438 Frankfurt am Main, Germany; Max Planck Institute for Biophysics, Max von Laue Strasse 3, 60438 Frankfurt am Main, Germany. Electronic address: julian.langer@brain.mpg.de.
authors.forename: Julian D
authors.initials: JD
authors.lastname: Langer
authors.affiliation: Max Planck Institute for Brain Research, Max von Laue Strasse 4, 60438 Frankfurt am Main, Germany; Max Planck Institute for Biophysics, Max von Laue Strasse 3, 60438 Frankfurt am Main, Germany. Electronic address: erin.schuman@brain.mpg.de.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Schuman
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000841:Anisomycin / Q000494:pharmacology; D000071437:Axon Guidance / Q000187:drug effects; D001640:Bicuculline / Q000494:pharmacology; D002478:Cells, Cultured; D002853:Chromatography, Liquid; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006706:Homeostasis; D000071446:Neuronal Outgrowth / Q000187:drug effects; D009473:Neuronal Plasticity; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D020543:Proteome / Q000187:drug effects / Q000378:metabolism*; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D058787:GABA-A Receptor Antagonists; D011500:Protein Synthesis Inhibitors; D020543:Proteome; D017470:Receptors, Glutamate; D000841:Anisomycin; D001640:Bicuculline
keywords: BONCAT; homeostatic scaling; protein synthesis; proteomics; synaptic plasticity; transcriptomics