PXD009920 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2018-05-25 08:30:24 | ID requested | |
⏵ 1 | 2018-07-11 06:48:44 | announced | |
Publication List
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] |
Keyword List
curator keyword: Biological |
submitter keyword: Nascentome, Neuronal-specific 20S membrane proteosome complex, translation, degradation |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/07/PXD009920 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD009920
- Label: PRIDE project
- Name: Activity-dependent degradation of the nascentome by the neuronal membrane proteosome