iRhom2 regulates ectodomain shedding and surface expression of the major histocompatibility complex (MHC) class I.
ADAM17
MHC class I molecules
Macrophages
Secretome
iRhom2
Journal
Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402
Informations de publication
Date de publication:
04 Apr 2024
04 Apr 2024
Historique:
received:
29
11
2023
accepted:
04
03
2024
revised:
22
02
2024
medline:
4
4
2024
pubmed:
4
4
2024
entrez:
3
4
2024
Statut:
epublish
Résumé
Proteolytic release of transmembrane proteins from the cell surface, the so called ectodomain shedding, is a key process in inflammation. Inactive rhomboid 2 (iRhom2) plays a crucial role in this context, in that it guides maturation and function of the sheddase ADAM17 (a disintegrin and metalloproteinase 17) in immune cells, and, ultimately, its ability to release inflammatory mediators such as tumor necrosis factor α (TNFα). Yet, the macrophage sheddome of iRhom2/ADAM17, which is the collection of substrates that are released by the proteolytic complex, is only partly known. In this study, we applied high-resolution proteomics to murine and human iRhom2-deficient macrophages for a systematic identification of substrates, and therefore functions, of the iRhom2/ADAM17 proteolytic complex. We found that iRhom2 loss suppressed the release of a group of transmembrane proteins, including known (e.g. CSF1R) and putative novel ADAM17 substrates. In the latter group, shedding of major histocompatibility complex class I molecules (MHC-I) was consistently reduced in both murine and human macrophages when iRhom2 was ablated. Intriguingly, it emerged that in addition to its shedding, iRhom2 could also control surface expression of MHC-I by an undefined mechanism. We have demonstrated the biological significance of this process by using an in vitro model of CD8
Identifiants
pubmed: 38570362
doi: 10.1007/s00018-024-05201-7
pii: 10.1007/s00018-024-05201-7
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
163Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM134907
Pays : United States
Informations de copyright
© 2024. The Author(s).
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