Details

Autor(en) / Beteiligte

• Benadda, Samira
• Nugue, Mathilde
• Koumantou, Despoina
• Bens, Marcelle
• De Luca, Mariacristina
• Pellé, Olivier
• Monteiro, Renato C.
• Evnouchidou, Irini
• Saveanu, Loredana

Titel

Activating FcγR function depends on endosomal-signaling platforms

Ist Teil von

• iScience, 2023-07, Vol.26 (7), p.107055-107055, Article 107055

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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 responsive aminopeptidase (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. [Display omitted] •Activated IgG receptors FcγRI and FcγRIIA are retained in IRAP+ endosomes•Activated IgA receptor FcαRI is targeted to lysosomes•At the endosomal level FcγRI is associated with the Syk, LAT, and PLCγ signaling proteins•IRAP deletion compromises FcγR-mediated cytokine secretion and ADCC Biological sciences; Immunology; Cell biology