PXD041161-1

PXD041161 is an original dataset announced via ProteomeXchange.

Title	An Abundance of Free Proteasomal Regulatory (19S) Particles Regulate Neuronal Synapses Independent of the Proteasome
Description	The major protein-degradation machine, the proteasome, functions at brain synapses and regulates long-term information storage. Here we found that the two essential subcomplexes of the proteasome, the regulatory (19S) and catalytic (20S) particles that assemble to recognize and degrade substrates, were differentially distributed within individual rat cortical neurons. By detecting and quantifying 19 and 20S particles at single-molecule resolution, we discovered a surprising abundance of free regulatory particles (19S) near synapses. Furthermore, we found that the free neuronal 19S binds and deubiquitylates Lys63-ubiquitin, a distinct ubiquitin linkage that does not target substrates to the proteasome. Pull-down assays for Lys63 or Lys48 ubiquitin revealed a significant over-representation of synaptic molecules as Lys63 interactors, while conventional proteasome-related proteins dominated the Lys48 interactome. Inhibition of 19S deubiquitylase (DUB) activity significantly altered spontaneous excitatory synaptic transmission and reduced the synaptic availability of AMPA receptors at multiple trafficking points in a proteasome-independent manner. Together, these results reveal a moonlighting function of the regulatory proteasomal subcomplex near synapses.
HostingRepository	PRIDE
AnnounceDate	2024-11-26
AnnouncementXML	Submission_2024-11-26_04:05:35.930.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	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-28 04:09:37	ID requested
⏵ 1	2024-11-26 04:05:36	announced

10.1126/science.adf2018;

Sun C, Desch K, Nassim-Assir B, Giandomenico SL, Nemcova P, Langer JD, Schuman EM, ) proteasome particles regulates neuronal synapses. Science, 380(6647):eadf2018(2023) [pubmed]

submitter keyword: K48, in-gel digest, synapse, neurons, neuronal proteasome, native PAGE, 19S, K63, proteasome,ubiquitin

Julian D. Langer
contact affiliation	Max Planck Institute for Brain Research Max Planck Institute of Biophysics
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

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/2024/11/PXD041161

PRIDE project URI

• PRIDE
  1. PXD041161
     1. Label: PRIDE project
     2. Name: An Abundance of Free Proteasomal Regulatory (19S) Particles Regulate Neuronal Synapses Independent of the Proteasome