Publication
Title
The y-secretase substrate proteome and its role in cell signaling regulation
Author
Abstract
y-Secretases mediate the regulated intramembrane proteolysis (RIP) of more than 150 integral membrane proteins. We developed an unbiased y-secretase substrate identification (G-SECSI) method to study to what extent these proteins are processed in parallel. We demonstrate here parallel processing of at least 85 membrane proteins in human microglia in steady-state cell culture conditions. Pharmacological inhibition of y-secretase caused substantial changes of human microglial transcriptomes, including the expression of genes related to the disease-associated microglia (DAM) response described in Alzheimer disease (AD). While the overall effects of y-secretase deficiency on transcriptomic cell states remained limited in control conditions, exposure of mouse microglia to AD-inducing amyloid plaques strongly blocked their capacity to mount this putatively protective DAM cell state. We conclude that y-secretase serves as a critical signaling hub integrating the effects of multiple extracellular stimuli into the overall transcriptome of the cell.
Language
English
Source (journal)
Molecular cell. - Cambridge, Mass.
Publication
Cambridge : Cell press , 2023
ISSN
1097-2765
DOI
10.1016/J.MOLCEL.2023.10.029
Volume/pages
83 :22 (2023) , p. 4106-4122.e10
ISI
001149590100001
Pubmed ID
37977120
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Project info
Xenotransplantation of iPSC derived microglia to decipher the impact of Progranulin in neuroinflammation and neurodegeneration.
Deciphering the microglia-neuron interactions in human Alzheimer's disease.
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identifier
Creation 04.03.2024
Last edited 08.03.2024
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