Activating FcγR function depends on endosomal-signaling platforms.
Biological sciences
Cell biology
Immunology
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
21 Jul 2023
21 Jul 2023
Historique:
received:
12
10
2022
revised:
02
04
2023
accepted:
01
06
2023
medline:
26
6
2023
pubmed:
26
6
2023
entrez:
26
6
2023
Statut:
epublish
Résumé
Cell surface receptor internalization can either terminate signaling or activate alternative endosomal signaling pathways. We investigated here whether endosomal signaling is involved in the function of the human receptors for Fc immunoglobulin fragments (FcRs): FcαRI, FcγRIIA, and FcγRI. All these receptors were internalized after their cross-linking with receptor-specific antibodies, but their intracellular trafficking was different. FcαRI was targeted directly to lysosomes, while FcγRIIA and FcγRI were internalized in particular endosomal compartments described by the insulin esponsive minoeptidase (IRAP), where they recruited signaling molecules, such as the active form of the kinase Syk, PLCγ and the adaptor LAT. Destabilization of FcγR endosomal signaling in the absence of IRAP compromised cytokine secretion downstream FcγR activation and macrophage ability to kill tumor cells by antibody-dependent cell-mediated cytotoxicity (ADCC). Our results indicate that FcγR endosomal signaling is required for the FcγR-driven inflammatory reaction and possibly for the therapeutic action of monoclonal antibodies.
Identifiants
pubmed: 37360697
doi: 10.1016/j.isci.2023.107055
pii: S2589-0042(23)01132-X
pmc: PMC10285637
doi:
Types de publication
Journal Article
Langues
eng
Pagination
107055Informations de copyright
© 2023 The Author(s).
Déclaration de conflit d'intérêts
The authors declare that they have no conflict of interest.
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