Single molecule tracking unveils distinct FcγRIIB and FcRn plasma membrane dynamics

Year: 2025

Authors: Rojas-Rodrnguez M., Pavone F.S., Calamai M.

Autors Affiliation: European Lab Nonlinear Spect, Via Nello Carrara 1, I-50019 Sesto Fiorentino, Italy; Univ Florence, Dept Phys & Astron, Via G Sansone 1, I-50019 Sesto Fiorentino, Italy; CNR, Natl Inst Opt, Natl Res Council, INO, Via Nello Carrara 1, I-50019 Sesto Fiorentino, Italy.

Abstract: Fc receptors (FcRs) constitute a heterogeneous family of membrane-bound proteins that are integral to the immune system function, primarily through their ability to bind the constant domain (Fc) of antibodies. These receptors mediate a variety of immunological processes and maintain immunological homeostasis. FcRs exhibit a broad distribution throughout the body, being expressed not only on the surface of various immune cells but also in non-immune cells and tissues. Over the past decade, specific FcRs-most notably the neonatal Fc receptor (FcRn) and Fc gamma receptor IIb (Fc gamma RIIB)-have emerged as putative mediators in processes such as antibody-mediated uptake. However, the literature presents conflicting evidence regarding their precise roles and mechanisms in antibody internalization. In this study, we employed single molecule tracking in living epithelial-like cells to investigate the cellular distribution and dynamics of Fc gamma RIIB and FcRn, basic features that are still largely uncharacterized. Our findings revealed that Fc gamma RIIB, mostly present on the cell membrane, is highly mobile and can be actively internalized. Conversely, FcRn was primarily localized intracellularly, with only a minor fraction capable of reaching the cell surface, where it exhibited minimal mobility. These results show that Fc gamma RIIB, but not FcRn, displays the basic expected requisites that would be necessary for surface antibody binding and uptake.

Journal/Review: ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS

Volume: 774      Pages from: 110628-1  to: 110628-12

More Information: This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 956977.
KeyWords: Fc receptors; Cellular distribution; Single molecule; Diffusion; Trafficking
DOI: 10.1016/j.abb.2025.110628