<<< Full experiment listing

PXD036906

PXD036906 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleProteomic datasets from sacsin knockout human SH-SY5Y and mouse primary cortical neurons
DescriptionAutosomal 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.
HostingRepositoryPRIDE
AnnounceDate2022-10-25
AnnouncementXMLSubmission_2022-10-25_09:55:09.616.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterLauraHerring
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListphosphorylated residue
InstrumentQ Exactive HF; Orbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-09-21 14:49:17ID requested
12022-10-25 09:55:09announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: neurobiology, ARSCACS, proteome, kinome,phosphoproteome, surfaceome
Contact List
JustinWolter
contact affiliationUNC Neuroscience Center, Cell Biology and Physiology, The University of North Carolina at Chapel Hill
contact emailjustin_wolter@med.unc.edu
lab head
LauraHerring
contact affiliationUNC-Chapel Hill
contact emaillaura_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
[ + ]