PXD039238

PXD039238 is an original dataset announced via ProteomeXchange.

Title	The γ-secretase substrate proteome and its role in cell signaling regulation
Description	γ-Secretase is involved in the regulated intramembrane proteolysis (RIP) of a variety of integral membrane proteins and generates the amyloid peptide (Aβ) in Alzheimer’s Disease (AD). Microglia are centrally involved in AD, but the substrates and function of γ-secretase in these cells remain largely unstudied. Using a novel γ-Secretase Substrate Identification (G-SECSI) method, we identified 85 substrates, of which 59 were previously unknown, in stem cell derived microglia-like cells. More than 60% of those are signalling receptors possibly involved in cell state regulation. Inhibition of γ-secretase using Semagacestat or selective genetic knockout alters the expression of homeostatic (HM) and disease-associated (DAM) genes, in particular when microglia are exposed to amyloid plaques in vivo. Thus, γ-secretase regulates tonic signaling via a spectrum of substrates in microglia in steady state, and its blockage results in the defective transition to the DAM response in AD.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:14:12.337.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andrew Howden
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2023-01-04 03:42:47	ID requested
1	2023-11-14 05:59:28	announced
⏵ 2	2024-10-22 06:14:12	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: gamma secretase, Alzheimer’s Disease,microglia

Bart De
contact affiliation	Laboratory for the Research of Neurodegenerative Diseases, VIB Center for Brain & Disease Research, VIB, Leuven, Belgium
contact email	Bart.destrooper@kuleuven.be
lab head
Andrew Howden
contact affiliation	University of Dundee
contact email	a.howden@dundee.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD039238
     1. Label: PRIDE project
     2. Name: The γ-secretase substrate proteome and its role in cell signaling regulation