Trafficking of interleukin 2 and transferrin in endosomal fractions of T lymphocytes.
The T lymphocyte growth factor interleukin 2 binds to surface high-affinity receptors and is rapidly internalized and degraded in acidic organelles. The alpha and beta chains of high-affinity interleukin 2 receptors are internalized together with interleukin 2. To identify the intracellular pathway followed by interleukin 2, we have compared the subcellular distribution of interleukin 2, transferrin and a fluid-phase marker, horseradish peroxidase, in the human T cell line IARC 301.5. Transferrin was used as a marker of early and recycling endosomes, and horseradish peroxidase to probe for the whole endocytic pathway. Fractionation of intracellular organelles on a discontinuous sucrose gradient showed that internalized interleukin 2 is initially mostly found in compartments with similar densities to transferrin, e.g. early and recycling endosomes. The kinetics of entry and exit of interleukin 2 from such organelles was much slower than that of transferrin. Later on, interleukin 2 is predominantly found in dense lysosome-containing fractions. Very little, if any, interleukin 2 was found in fractions corresponding to late endosomes containing horseradish peroxidase. These results suggest that, after endocytosis, interleukin 2 enters early or recycling endosomes before it reaches dense lysosomes.
Duprez
V
V
Unité de Biologie des Interactions Cellulaires, CNRS URA 361, Institut Pasteur, Paris, France.
Smoljanovic
M
M
Lieb
M
M
Dautry-Varsat
A
A
D015415:Biomarkers; D002451:Cell Compartmentation; D002460:Cell Line; D011992:Endosomes / Q000378:metabolism; D006735:Horseradish Peroxidase / Q000493:pharmacokinetics; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D007700:Kinetics; D008247:Lysosomes / Q000378:metabolism; D015335:Molecular Probes; D013347:Subcellular Fractions / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism*
D015415:Biomarkers; D007376:Interleukin-2; D015335:Molecular Probes; D014168:Transferrin; D006735:Horseradish Peroxidase