title: Endocytosis of interleukin 2 receptors in human T lymphocytes: distinct intracellular localization and fate of the receptor alpha, beta, and gamma 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 interleukin (IL) 2 and IL15 have common beta and gamma chains, while those for IL2, 4, 7, and 9 have a common gamma 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 alpha, beta, and gamma chains had different intracellular localizations after being endocytosed together. The alpha 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 beta and gamma chains were excluded from transferrin-positive organelles and did not colocalize with alpha. Furthermore, beta could be found in rab7-positive vesicles. These differences suggest that the alpha chain recycles to the plasma membrane, while the beta and gamma chains are 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 beta and gamma chains are very short-lived polypeptides since their half-life on the surface is only approximately 1 h, whereas alpha 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.
authors.affiliation: Unité de Biologie des Interactions Cellulaires, URA CNRS 1960, Institut Pasteur, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Hémar
authors.forename: A
authors.initials: A
authors.lastname: Subtil
authors.forename: M
authors.initials: M
authors.lastname: Lieb
authors.forename: E
authors.initials: E
authors.lastname: Morelon
authors.forename: R
authors.initials: R
authors.lastname: Hellio
authors.forename: A
authors.initials: A
authors.lastname: Dautry-Varsat
mesh_terms: D000911:Antibodies, Monoclonal; D002999:Clone Cells; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D007457:Iodine Radioisotopes; D007700:Kinetics; D046911:Macromolecular Substances; D018613:Microscopy, Confocal; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D007457:Iodine Radioisotopes; D046911:Macromolecular Substances; D015375:Receptors, Interleukin-2