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- Cytokine receptor cluster size impacts its endocytosis and signaling
Cytokine receptor cluster size impacts its endocytosis and signaling
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.