PXD004889

PXD004889 is an original dataset announced via ProteomeXchange.

Title	Nascent Proteome Remodeling following Homeostatic Scaling at Hippocampal Synapses.
Description	Neuronal networks are subject to fluctuations in both the magnitude and frequency of inputs, requiring plasticity mechanisms to stabilize network activity. Homeostatic synaptic scaling is a form of synaptic plasticity that adjusts the strength of neuronal connections up or down in response to large changes in input. Although homeostatic plasticity requires changes in gene expression, there is only limited data describing the molecular changes associated with homeostatic scaling, focusing mostly on the expression mechanisms involving glutamate receptors. The fact that neuronal networks can be scaled up (in response to reduced activity) or down (in response to enhanced activity) provides a unique opportunity to examine the molecular and proteomic response to opposite ends of the phenotypic spectrum of synaptic plasticity. Here we first demonstrate that homeostatic scaling required protein synthesis. We then examined the plasticity-induced changes in the newly-synthesized neuronal proteome of neurons to identify the landscape of proteomic changes that contribute to opposing forms of homeostatic plasticity. Cultured rat hippocampal neurons (21 DIV) underwent homeostatic upscaling or downscaling (treatments with TTX and Bicucculine, respectively). We used BONCAT (BioOrthogonal Non-Canonical Amino acid Tagging) to metabolically label, capture and identify newly-synthesized proteins, detecting and analysing 5940 newly-synthesized proteins using liquid chromatography-coupled tandem mass spectrometry and label-free quantitation. Neither up- or down-scaling produced changes in the number of different proteins translated. Rather, our findings indicate that synaptic up- and down-scaling elicit opposing translational regulation of several molecular pathways, producing targeted adjustments in the neuronal proteome. We detected ~ 300 differentially regulated proteins involved in neurite outgrowth, reorganization of nerve terminals, axon guidance and targeting, neurotransmitter transport, filopodia assembly, excitatory synapses and glutamate receptor complexes. These proteins include well-characterized mediators of synaptic plasticity, e.g. the ionotropic glutamate receptor complex that is down-regulated during down-scaling and coordinately upregulated during upscaling. We also identified differentially regulated proteins that in addition to their regulation in homeostatic plasticity, are also associated with multiple diseases and disorders, including intellectual disability, schizophrenia, epilepsy, and Parkinson’s disease.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:32:32.470.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Julian Langer
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	acetylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2016-08-23 06:00:35	ID requested
1	2017-01-03 03:22:05	announced
2	2017-10-24 03:24:18	announced	Updated project metadata.
⏵ 3	2024-10-22 04:32:36	announced	2024-10-22: Updated project metadata.

Schanzenb, ä, cher CT, Sambandan S, Langer JD, Schuman EM, Nascent Proteome Remodeling following Homeostatic Scaling at Hippocampal Synapses. Neuron, 92(2):358-371(2016) [pubmed]

10.1016/j.neuron.2016.09.058;

curator keyword: Biological, Biomedical

submitter keyword: Synaptic plasticity, Q Exactive Plus, Homeostatic scaling, LFQ

Julian Langer
contact affiliation	MPI for Biophysics MPI for Brain Research Max von Laue Strasse 3/4 Frankfurt am Main
contact email	julian.langer@biophys.mpg.de
lab head
Julian Langer
contact affiliation	MPIs for Biophysics and Brain Research
contact email	julian.langer@biophys.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD004889
     1. Label: PRIDE project
     2. Name: Nascent Proteome Remodeling following Homeostatic Scaling at Hippocampal Synapses.