PXD009920

PXD009920 is an original dataset announced via ProteomeXchange.

Title	Activity-dependent degradation of the nascentome by the neuronal membrane proteosome
Description	Activity-dependent changes in neuronal function require coordinated regulation of the protein synthesis and protein degradation machinery to maintain protein homeostasis, critical to proper neuronal function. However, the biochemical evidence for this balance and coordination remains poorly understood and largely underexplored. Leveraging our recent discovery of a neuronal-specific 20S membrane proteasome complex (NMP), we began exploring how neuronal activity regulates its function. Remarkably, we observed polypeptides being synthesized during neuronal stimulation were rapidly turned over by the NMP. This turnover correlated with enhanced production of NMP-derived peptides in the extracellular space. Using parameters determined in these experiments, we constructed Markov process chain models in silico which predicted that the kinetics of this process necessitate coordination of translation and degradation. In a series of biochemical analyses, this predicted coordination was instantiated by NMP-mediated and ubiquitin-independent degradation of ribosome-associated nascent polypeptides. Using in-depth, global, and unbiased mass spectrometry, we identified the nascent protein substrates of the NMP. Among these substrates, we found that immediate-early gene products c-Fos and Npas4 were targeted to the NMP during ongoing activity-dependent protein synthesis, prior to activity-induced transcriptional responses. We propose that these findings generally define an activity-dependent protein homeostasis program through the NMP that selectively targets nascent polypeptides prior to adopting their final functional conformations.
HostingRepository	PRIDE
AnnounceDate	2018-07-11
AnnouncementXML	Submission_2018-07-11_06:48:43.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	chanhyun na
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-05-25 08:30:24	ID requested
⏵ 1	2018-07-11 06:48:44	announced

Ramachandran KV, Fu JM, Schaffer TB, Na CH, Delannoy M, Margolis SS, Activity-Dependent Degradation of the Nascentome by the Neuronal Membrane Proteasome. Mol Cell, 71(1):169-177.e6(2018) [pubmed]

curator keyword: Biological

submitter keyword: Nascentome, Neuronal-specific 20S membrane proteosome complex, translation, degradation

Seth Margolis
contact affiliation	Johns Hopkins School of Medicine Department of Biological Chemistry Woods Basic Science Building Room 517 725 N. Wolfe St. Baltimore, MD 21205, USA
contact email	smargol7@jhmi.edu
lab head
chanhyun na
contact affiliation	Johns Hopkins University
contact email	chanhyun.na@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD009920
     1. Label: PRIDE project
     2. Name: Activity-dependent degradation of the nascentome by the neuronal membrane proteosome