PXD008619 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Surface glycoproteome of BACE1-inhibited neurons |
Description | The 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. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_04:06:33.899.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Stephan Mueller |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue |
Instrument | LTQ Orbitrap Velos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2018-01-09 00:01:26 | ID requested | |
1 | 2018-05-08 05:51:37 | announced | |
⏵ 2 | 2024-10-22 04:06:42 | announced | 2024-10-22: 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 affiliation | German Center for Neurodegenerative Diseases (DZNE) Munich |
contact email | stefan.lichtenthaler@dzne.de |
lab head | |
Stephan Mueller |
contact affiliation | DZNE Munich Neuroproteomics |
contact email | stephan.mueller@dzne.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD008619
- Label: PRIDE project
- Name: Surface glycoproteome of BACE1-inhibited neurons