Interleukin 2 Receptors and Detergent-Resistant Membrane Domains Define a Clathrin-Independent Endocytic Pathway

• Published in: Molecular cell Vol. 7; no. 3; pp. 661 - 671
• Main Authors: Lamaze, Christophe, Dujeancourt, Annick, Baba, Takeshi, Lo, Charles G, Benmerah, Alexandre, Dautry-Varsat, Alice
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2001; Cell Press
• Subjects: Adaptor Proteins, Signal Transducing; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - metabolism; Cell Line; Cellular Biology; clathrin; Clathrin - metabolism; Coated Pits, Cell-Membrane - metabolism; Detergents - pharmacology; Development Biology; Drug Resistance; Dynamins; Endocytosis - drug effects; Genetics; GTP Phosphohydrolases - genetics; GTP Phosphohydrolases - metabolism; HeLa Cells; Human health and pathology; Humans; interleukin 2 receptors; Interleukin-2 - pharmacology; Intracellular Signaling Peptides and Proteins; Life Sciences; Lymphocytes - cytology; Lymphocytes - drug effects; Lymphocytes - metabolism; Lymphocytes - ultrastructure; Membrane Microdomains - drug effects; Membrane Microdomains - metabolism; Microscopy, Electron; Mutation - genetics; Octoxynol - pharmacology; Phosphoproteins - genetics; Phosphoproteins - metabolism; Receptors, Interleukin-2 - metabolism; Receptors, Transferrin - metabolism; rho GTP-Binding Proteins - genetics; rho GTP-Binding Proteins - metabolism; Rho protein; Transfection; transferrin; Urology and Nephrology
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/S1097-2765(01)00212-X

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.