Interleukin 2 receptors and detergent-resistant membrane domains define a clathrin-independent endocytic pathway.
Clathrin-dependent endocytosis has long been presented as the only efficient mechanism by which transmembrane receptors are internalized. We selectively blocked this process using dominant-negative mutants of Eps15 and showed that clathrin-mediated endocytosis of transferrin was inhibited, while endocytosis of interleukin 2 (IL2) receptors proceeded normally. Ultrastructural and biochemical experiments showed that clathrin-independent endocytosis of IL2 receptors exists constitutively in lymphocytes and is coupled to their association with detergent-resistant membrane domains. Finally, clathrin-independent endocytosis requires dynamin and is specifically regulated by Rho family GTPases. These results define novel properties of receptor-mediated endocytosis and establish that the IL2 receptor is efficiently internalized through this clathrin-independent pathway.
Lamaze
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Unité de Biologie des Interactions Cellulaires, URA CNRS 1960, Institut Pasteur, Paris, France. clamaze@pasteur.fr
Dujeancourt
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Baba
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Lo
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Benmerah
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Dautry-Varsat
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D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002966:Clathrin / Q000378:metabolism*; D003034:Coated Pits, Cell-Membrane / Q000378:metabolism; D003902:Detergents / Q000494:pharmacology*; D004351:Drug Resistance; D034281:Dynamins; D004705:Endocytosis / Q000187:drug effects; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D021962:Membrane Microdomains / Q000187:drug effects* / Q000378:metabolism*; D008854:Microscopy, Electron; D009154:Mutation / Q000235:genetics; D017830:Octoxynol / Q000494:pharmacology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism; D014162:Transfection; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; D002966:Clathrin; D003902:Detergents; C486206:EPS15 protein, human; D007376:Interleukin-2; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D015375:Receptors, Interleukin-2; D011990:Receptors, Transferrin; D017830:Octoxynol; D020558:GTP Phosphohydrolases; D020741:rho GTP-Binding Proteins; D034281:Dynamins