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

Clathrin-dependent endocytosis has long been presented as the only efficien t mechanism by which transmembrane receptors are internalized. We selective ly blocked this process using dominant-negative mutants of Eps15 and showed that clathrin-mediated endocytosis of transferrin was inhibited, while end ocytosis of interleukin 2 (IL2) receptors proceeded normally. Ultrastructur al and biochemical experiments showed that clathrin-independent endocytosis of IL2 receptors exists constitutively in lymphocytes and is coupled to th eir association with detergent-resistant membrane domains. Finally, clathri n-independent endocytosis requires dynamin and is specifically regulated by Rho family GTPases. These results define novel properties of receptor-medi ated endocytosis and establish that the IL2 receptor is efficiently interna lized through this clathrin-independent pathway.