⮝ Full datasets listing

PXD021396

PXD021396 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleCNS-derived extracellular vesicles from superoxide dismutase 1 (SOD1)G93A ALS mice originate from astrocytes and neurons and carry misfolded SOD1
DescriptionExtracellular vesicles (EVs) are secreted by myriad cells in culture and also by unicellular organisms, and their identification in mammalian fluids suggests that EV release also occurs at the organism level. However, although it is clearly important to better understand EVs' roles in organismal biology, EVs in solid tissues have received little attention. Here, we modified a protocol for EV isolation from primary neural cell culture to collect EVs from frozen whole murine and human neural tissues by serial centrifugation and purification on a sucrose gradient. Quantitative proteomics comparing brain-derived EVs from nontransgenic (NTg) and a transgenic amyotrophic lateral sclerosis (ALS) mouse model, superoxide dismutase 1 (SOD1) G93A , revealed that these EVs contain canonical exosomal markers and are enriched in synaptic and RNA-binding proteins. The compiled brain EV proteome contained numerous proteins implicated in ALS, and EVs from SOD1 G93A mice were significantly depleted in myelin-oligodendrocyte glycoprotein compared with those from NTg animals. We observed that brain- and spinal cord–derived EVs, from NTg and SOD1 G93A mice, are positive for the astrocyte marker GLAST and the synaptic marker SNAP25, whereas CD11b, a microglial marker, was largely absent. EVs from brains and spinal cords of the SOD1 G93A ALS mouse model, as well as from human SOD1 familial ALS patient spinal cord, contained abundant misfolded and nonnative disulfide-cross-linked aggregated SOD1. Our results indicate that CNS-derived EVs from an ALS animal model contain pathogenic disease-causing proteins and suggest that brain astrocytes and neurons, but not microglia, are the main EV source.
HostingRepositoryPRIDE
AnnounceDate2020-09-11
AnnouncementXMLSubmission_2020-09-10_22:42:18.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJenny Moon
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListNo PTMs are included in the dataset
InstrumentBruker Daltonics instrument model
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-09-10 01:38:26ID requested
12020-09-10 22:42:18announced
Publication List
Silverman JM, Christy D, Shyu CC, Moon KM, Fernando S, Gidden Z, Cowan CM, Ban Y, Stacey RG, Grad LI, McAlary L, Mackenzie IR, Foster LJ, Cashman NR, ALS mice originate from astrocytes and neurons and carry misfolded SOD1. J Biol Chem, 294(10):3744-3759(2019) [pubmed]
Keyword List
submitter keyword: exosome (vesicle), amyotrophic lateral sclerosis (ALS) (Lou Gehrig disease), neurodegeneration, proteomics, astrocyte, extracellular vesicles, central nervous system (CNS), secretion, protein homeostasis, mouse model
Contact List
Neil R. Cashman
contact affiliationCentre for Brain Health, Dept. of Medicine, University of British Columbia, Vancouver, British Columbia V6T 1B5, Canada
contact emailneil.cashman@vch.ca
lab head
Jenny Moon
contact affiliationUniversity of British Columbia
contact emailkyungmee@mail.ubc.ca
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/2020/09/PXD021396
PRIDE project URI
Repository Record List
[ + ]