PXD008619

PXD008619 is an original dataset announced via ProteomeXchange.

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

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.

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]

curator keyword: Biological

submitter keyword: BACE1, surface, N-glycoproteome, murine neurons

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

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/2018/05/PXD008619

PRIDE project URI

• PRIDE
  1. PXD008619
     1. Label: PRIDE project
     2. Name: Surface glycoproteome of BACE1-inhibited neurons