⮝ Full datasets listing
PXD073715
PXD073715 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | ESCRT-0 regulates AMPA receptor conductance and Ca2+- dependent signaling |
| Description | Membrane protein trafficking is essential for synaptic growth, maintenance, function, and plasticity and involves the regulated exocytosis and endocytosis of proteins to and from the pre- and post-synaptic membranes. Defects in membrane protein trafficking can lead to the accumulation of ubiquitinated membrane proteins and contribute to neurodegenerative disease. The ESCRT (endosomal sorting complexes required for transport) machinery binds and sorts ubiquitinated membrane proteins into lysosomes for degradation, yet the presence and function of ESCRTs in sorting ubiquitinated AMPA and other receptors at the post-synapse remain unclear. Here we show that the ubiquitin-binding ESCRT-0 protein, Hrs, localizes to both pre- and post-synapses, and levels are modulated by neuronal activity, increasing and decreasing with higher and lower neuronal activity, respectively. Phosphoproteomic profiling of Hrs-depleted post-synaptic membranes revealed a role for Hrs in glutamatergic synaptic transmission, including long-term potentiation. In addition, Hrs-depleted neurons showed faster AMPAR current kinetics and reduced amplitude in whole-cell patch-clamp recordings. Furthermore, genetic deletion of neuronal Hgs in mice led to reductions in phosphorylated CaMKII-alpha and -beta (T286/T287) and in the structural proteins, PSD-95 and gephyrin, suggestive of long-term depression (LTD)-like synaptic depression. Hrs overexpression led to increased Ca2+-responsive signaling, including phosphorylation of protein kinase C (PKC) substrates and AMPAR subunit GluA1-S831, which increases conductance. Together these findings identify a dynamic, bidirectional role for Hrs at the post-synapse as it both senses and is modulated by neuronal activity, ultimately impacting excitatory synaptic strength |
| HostingRepository | MassIVE |
| AnnounceDate | 2026-01-28 |
| AnnouncementXML | Submission_2026-01-28_14:28:02.669.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Daniel McClatchy |
| SpeciesList | scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090; |
| ModificationList | Phospho |
| Instrument | Orbitrap Eclipse |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2026-01-28 08:19:33 | ID requested | |
| ⏵ 1 | 2026-01-28 14:28:03 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: Synaptic Plasticity, long-term depression, membrane trafficking, ubiquitin-mediated sorting, DatasetType:Proteomics |
Contact List
| Christina Sigurdson | |
|---|---|
| contact affiliation | UC San Diego |
| contact email | csigurdson@health.ucsd.edu |
| lab head | |
| Daniel McClatchy | |
| contact affiliation | TSRI |
| contact email | dmcclat@scripps.edu |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| 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://massive-ftp.ucsd.edu/v12/MSV000100622/ |
