PXD051060-1
PXD051060 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Dysregulated Prion signaling induces calcium influx, protein kinase C activation, and NMDA receptor dependent excitotoxicity |
| Description | Neuronal hyperexcitability precedes synapse loss in certain neurodegenerative diseases, yet the synaptic membrane interactions and downstream signaling events remain unclear. The disordered amino terminus of the prion protein (PrPC) has been implicated in aberrant signaling in prion and Alzheimer’s disease. To disrupt neuronal interactions and signaling linked to the amino terminus, we CRISPR-engineered a knockin mouse expressing mutant PrPC (G92N), generating an N-linked glycosylation site between 2 functional motifs. Mice developed seizures and necrosis of hippocampal pyramidal neurons, similar to prion-infected mice and consistent with excitotoxicity. Phosphoproteomics analysis revealed phosphorylated glutamate receptors and calcium-sensitive kinases, including protein kinase C (PKC). Additionally, 92N-PrPC-expressing neurons showed persistent calcium influx as well as dendritic beading, which was rescued by an N-methyl-d-aspartate receptor (NMDAR) antagonist. Finally, survival of Prnp92N mice was prolonged by blocking active NMDAR channels. We propose that dysregulated PrPC/NMDAR-induced signaling can trigger an excitatory, inhibitory imbalance, spongiform degeneration, and neurotoxicity and that calcium dysregulation is central to PrPC-linked neurodegeneration. |
| HostingRepository | MassIVE |
| AnnounceDate | 2025-04-22 |
| AnnouncementXML | Submission_2025-04-22_12:13:46.554.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 Fusion Lumos |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2024-03-28 08:23:53 | ID requested | |
| ⏵ 1 | 2025-04-22 12:13:46 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: glycans, neuron |
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/v07/MSV000094427/ |
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