Cytokine receptor cluster size impacts its endocytosis and signaling

14 sept. 2021Proceedings of the National Academy of Sciences

DOI : 10.1073/pnas.2024893118

Auteurs

Laura Salavessa, Thibault Lagache, Valérie Malardé, Alexandre Grassart, Jean-Christophe Olivo-Marin, Alexis Canette, Michael Trichet, Philippe J. Sansonetti, Nathalie Sauvonnet

Résumé

Significance

The IL-2R is a key receptor of the immune system, promoting both immunity and tolerance through activation of signaling cascades on lymphocytes. This receptor induces responses that include T cell expansion, development and suppression of autoreactive lymphocytes, being critical in the prevention of autoimmune diseases. These functions are regulated by the internalization and intracellular trafficking of IL-2R, which undergoes a coat-independent mechanism of endocytosis. Our work shows that clustering of IL-2R at the cell surface is fundamental in the efficient internalization of the receptor and that an optimal cluster size is required for this. Disorganization of IL-2R clustering, through perturbation of the actin cytoskeleton or membrane cholesterol, affects endocytosis and modifies IL-2–induced signaling.