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PXD008619

PXD008619 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSurface glycoproteome of BACE1-inhibited neurons
DescriptionThe cell surface proteome is dynamic and has fundamental roles in cell signaling. Many surface membrane proteins are proteolytically released into a cell’s secretome, where they can have additional functions in cell-cell-communication. Yet, it remains challenging to determine the surface proteome and to compare it to the cell secretome, in particular under serum-containing cell culture conditions. Here, we set-up and evaluated the ‘surface-spanning protein enrichment with click sugars’ (SUSPECS) method for cell surface membrane glycoprotein biotinylation, enrichment and label-free quantitative mass spectrometry. SUSPECS is based on click chemistry-mediated labeling of glycoproteins, is fully compatible with labeling of living cells and can be combined with secretome analyses in the same experiment. Immunofluorescence-based confocal microscopy demonstrated that SUSPECS selectively labeled proteins at the cell surface, but not within cells. Nearly 700 transmembrane glycoproteins were quantified at the surface of primary murine neurons. To demonstrate the utility of SUSPECS, we tested how the protease BACE1, which is a key drug target in Alzheimer’s disease, affects the cell surface glycoproteome. Pharmacological inhibition of BACE1 selectively remodeled the neuronal surface proteome, resulting in up to seven-fold increased abundance of the BACE1 substrates APP, SEZ6, SEZ6L, CNTN2, CHL1 and L1, while other substrates were not or only mildly affected. Protein changes at the cell surface only partly correlated with changes in the secretome. Additionally, apparent non-substrates, such as TSPAN6, were also increased. Several altered proteins were validated by immunoblots in neurons and BACE1-deficient murine brains and indicate that BACE1-inhibition may lead to unexpected secondary effects.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:06:33.899.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterStephan Mueller
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListmonohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
InstrumentLTQ Orbitrap Velos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-01-09 00:01:26ID requested
12018-05-08 05:51:37announced
22024-10-22 04:06:42announced2024-10-22: Updated project metadata.
Publication List
10.1074/mcp.ra118.000608;
Herber J, Njavro J, Feederle R, Schepers U, M, ü, ller UC, Br, ä, se S, M, ü, ller SA, Lichtenthaler SF, Click Chemistry-mediated Biotinylation Reveals a Function for the Protease BACE1 in Modulating the Neuronal Surface Glycoproteome. Mol Cell Proteomics, 17(8):1487-1501(2018) [pubmed]
Keyword List
curator keyword: Biological
submitter keyword: BACE1, surface, N-glycoproteome, murine neurons
Contact List
Stefan Lichtenthaler
contact affiliationGerman Center for Neurodegenerative Diseases (DZNE) Munich
contact emailstefan.lichtenthaler@dzne.de
lab head
Stephan Mueller
contact affiliationDZNE Munich Neuroproteomics
contact emailstephan.mueller@dzne.de
dataset submitter
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Dataset FTP location
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PRIDE project URI
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