RAPID ENDOCYTOSIS OF INTERLEUKIN-2 RECEPTORS WHEN CLATHRIN-COATED PITENDOCYTOSIS IS INHIBITED

The cytokine interleukin 2 (IL2) is produced by activated helper T lym phocytes and modulates the growth and activity of cells expressing hig h-affinity surface IL2 receptors that transduce its signaling, After l igand binding to receptors on the plasma membrane, receptor-ligand com plexes are rapidly endocytosed and IL2 is degraded in acidic compartme nts, The best known receptor-mediated endocytosis pathway involves cla thrin-coated pits. Receptors that carry an internalization signal reco gnized by adaptors on the cytosolic side of the plasma membrane are cl ustered into the coated pits and enter cells very efficiently. Many re ceptors use this pathway, but other endocytic pathways have also been reported, for ricin, EGF and insulin, for instance, which seem to be l ess efficient than the coated one. We compared the endocytosis of IL2 and its receptors to that of transferrin, a marker of the coated pit p athway. Under normal conditions, the kinetics of entry of IL2 was two times slower than that of transferrin, When internalization via coated pits was inhibited by two different methods, potassium depletion and cytosol acidification, endocytosis of IL2 and its receptors was only p artly inhibited, while transferrin entry was strongly affected, Treatm ent with the cationic amphiphilic drug chlorpromazine, which induces a redistribution of a clathrin-coated pit component, AP-2, to endosomes , reduced transferrin, but not IL2 internalization. Thus, unexpectedly , this cytokine and its receptors can still be rapidly endocytosed in the absence of functional clathrin-coated structures, We propose a mod el for receptor-mediated endocytosis that may account for these result s and published data on other receptors.