Activating FcγR function depends on endosomal-signaling platforms

• DOI: 10.1016/j.isci.2023.107055
• Publication Date: 2023-06-09T02:34:56Z
• Authors: Samira Benadda; Mathilde Nugue; Despoina Koumantou; Marcelle Bens; Mariacristina De ...; Olivier Pellé; Renato C. Monteiro; Irini Evnouchidou; Loredana Saveanu
• Keywords: Internalization; Fc receptor; Cell Signaling

Cell surface receptor internalization can either terminate signaling or activate alternative endosomal pathways. We investigated here whether is involved in the function of human receptors for Fc immunoglobulin fragments (FcRs): FcαRI, FcγRIIA, and FcγRI. All these were internalized after their cross-linking with receptor-specific antibodies, but intracellular trafficking was different. FcαRI targeted directly to lysosomes, while FcγRIIA FcγRI particular compartments described by insulin esponsive minoeptidase (IRAP), where they recruited molecules, such as active form kinase Syk, PLCγ adaptor LAT. Destabilization FcγR absence IRAP compromised cytokine secretion downstream activation macrophage ability kill tumor cells antibody-dependent cell-mediated cytotoxicity (ADCC). Our results indicate that required FcγR-driven inflammatory reaction possibly therapeutic action monoclonal antibodies.