PXD036906 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Proteomic datasets from sacsin knockout human SH-SY5Y and mouse primary cortical neurons |
Description | Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a childhood-onset cerebellar ataxia caused by mutations in SACS, which encodes the protein sacsin. Cellular ARSACS phenotypes include mitochondrial dysfunction, intermediate filament disorganization, and the progressive death of cerebellar Purkinje neurons. It is unclear how the loss of sacsin function causes these deficits, or why they manifest as cerebellar ataxia. Here, we performed multi-omic profiling in sacsin knockout (KO) cells, and identified alterations in microtubule dynamics, protein trafficking, and mislocalization of synaptic and focal adhesion proteins, including multiple integrins. Focal adhesion structure, signaling, and function were affected in KO cells, which could be rescued by reducing levels of PTEN, an overabundant negative regulator of focal adhesion signaling. Purkinje neurons in ARSACS mice possessed mislocalization of ITGA1, and disorganization of synaptic structures in the deep cerebellar nucleus (DCN). Interactome analysis revealed that sacsin regulates protein-protein interactions between structural and synaptic adhesion proteins. Our findings suggest that disrupted trafficking of synaptic adhesion proteins is a causal molecular deficit underlying ARSACS. |
HostingRepository | PRIDE |
AnnounceDate | 2022-10-25 |
AnnouncementXML | Submission_2022-10-25_09:55:09.616.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | LauraHerring |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | phosphorylated residue |
Instrument | Q Exactive HF; Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-09-21 14:49:17 | ID requested | |
⏵ 1 | 2022-10-25 09:55:09 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: neurobiology, ARSCACS, proteome, kinome,phosphoproteome, surfaceome |
Contact List
JustinWolter |
contact affiliation | UNC Neuroscience Center, Cell Biology and Physiology, The University of North Carolina at Chapel Hill |
contact email | justin_wolter@med.unc.edu |
lab head | |
LauraHerring |
contact affiliation | UNC-Chapel Hill |
contact email | laura_herring@med.unc.edu |
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/2022/10/PXD036906 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD036906
- Label: PRIDE project
- Name: Proteomic datasets from sacsin knockout human SH-SY5Y and mouse primary cortical neurons