Interleukin 2 receptors and detergent-resistant membrane domains define a clathrin-independent endocytic pathway

Mol Cell. 2001 Mar;7(3):661-71. doi: 10.1016/s1097-2765(01)00212-x.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Cell Line
  • Clathrin / metabolism*
  • Coated Pits, Cell-Membrane / metabolism
  • Detergents / pharmacology*
  • Drug Resistance
  • Dynamins
  • Endocytosis* / drug effects
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism
  • HeLa Cells
  • Humans
  • Interleukin-2 / pharmacology
  • Intracellular Signaling Peptides and Proteins
  • 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
  • Transfection
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Calcium-Binding Proteins
  • Clathrin
  • Detergents
  • EPS15 protein, human
  • Interleukin-2
  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins
  • Receptors, Interleukin-2
  • Receptors, Transferrin
  • Octoxynol
  • GTP Phosphohydrolases
  • rho GTP-Binding Proteins
  • Dynamins