New ProteomeXchange dataset PXD068396

[ProteomeCentral Agent]

Dear ProteomeXchange subscriber, a new ProteomeXchange dataset is being announced. To see more information, click here:

https://proteomecentral.proteomexchange.org/dataset/PXD068396

Summary of dataset

Status: new
Identifier: PXD068396
HostingRepository: MassIVE
Species: Homo sapiens
Title: PrPC-facilitated cell-signaling activates phospholipase Cgamma1 and triggers an Arc/Arg3.1 response in mouse neurons and human iPSC-derived neurons
Submitter: Daniel McClatchy
LabHead: Christina Sigurdson
Description: Synapse loss is an early feature of prion disease, yet the underlying drivers are poorly understood. We recently revealed evidence of neuronal hyperactivity in prion-infected animal models. Herein we identified increased Arc/Arg3.1 in patients with prion disease, suggesting heightened neuronal activity also occurs in human prion-affected brain. To determine the signaling events initiated by prion aggregates (PrPSc), we developed a disease model in which human iPSC-derived excitatory neurons (iNs) are stimulated with a PrPSc-mimetic antibody that binds the cellular prion protein. Within two hours, we detected an Arc response together with transcriptomic changes previously reported in prion-infected mice. Proteomics, RNA sequencing, and a phosphokinase array revealed altered phosphorylation changes of PLC-gamma1, ERK1/2, and EGFR as PrPC-triggered cell signaling events accompanying the Arc/Arg3.1 response. These results suggest that PrPC ligands, including PrPSc, may trigg
er rapid signaling events linked to neuronal hyperactivity in human neurons, and indicate PLC-gamma1 as a potential interventional target.

HTML_URL: https://proteomecentral.proteomexchange.org/dataset/PXD068396
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