Endocytosis of interleukin 2 receptors in human T lymphocytes: distinct intracellular localization and fate of the receptor alpha, beta, and gamma chains.
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.
Hémar
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A
Unité de Biologie des Interactions Cellulaires, URA CNRS 1960, Institut Pasteur, Paris, France.
Subtil
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Lieb
M
M
Morelon
E
E
Hellio
R
R
Dautry-Varsat
A
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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
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D007457:Iodine Radioisotopes; D046911:Macromolecular Substances; D015375:Receptors, Interleukin-2