Endocytosis of interleukin 2 receptors in human T lymphocytes: Distinct intracellular localization and fate of the receptor α, β, and γ chains

Abstract

Members of the cytokine receptor family are composed of several noncovalently linked chains with sequence and structure homologies in their extracellular domain. Receptor subfamily members share at least one component: thus the receptors for inter leukin (IL) 2 and IL15 have common β and γ chains, while those for IL2, 4, 7, and 9 have a common γ chain. The intracellular pathway followed by IL2 receptors after ligand binding and endocytosis was analyzed by immunofluorescence and confocal microscopy in a human T lymphocytic cell line. Surprisingly, the α, β, and γ chains had different intracellular localizations after being endocytosed together. The α chain was always in transferrin-positive compartments (early/recycling endosomes), both at early and late internalization times, but was never detected in rab7-positive compartments (late endosomes). On the other hand, at late internalization times, the β and γ chains were excluded from transferrin-positive organelles and did not colocalize with α. Furthermore, β could be found in rab7-positive vesicles. These differences suggest that the α chain recycles to the plasma membrane, while the β and γ chains am sorted towards the degradation pathway. The half-lives of these three chains on the cell surface also reflect their different intracellular fates after endocytosis. The β and γ chains are very short-lived polypeptides since their half-life on the surface is only ≃1 h, whereas α is a much more stable surface protein. This shows for the first time that components of a multimeric receptor can be sorted separately along the endocytic pathway.