Endocytosis of the Common Cytokine Receptor γcChain
IDENTIFICATION OF SEQUENCES INVOLVED IN INTERNALIZATION AND DEGRADATION*
- From the Unité de Biologie des Interactions Cellulaires, URA CNRS 1960, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France
Abstract
The common cytokine receptor γc, shared by interleukin 2, 4, 7, 9, and 15 receptors, has a major role in lymphocyte proliferation and differentiation, leading, when mutated, to a genetic disease, X-linked severe combined immunodeficiency. In this study, we report that γc is internalized and degraded in lymphoid cells. To identify γc regions involved in sorting along the endocytic pathway, we have studied a chimeric protein composed of the extracellular part of interleukin 2-receptor α and transmembrane and intracellular part of γc, αγγwt. When transfected in Jurkat T cells, αγγwt is as efficiently internalized and degraded as γc, demonstrating that the transmembrane and cytosolic tail of γc carry sequences involved in this process. To identify these motifs, we have analyzed the trafficking of chimeric proteins with serial truncations in their cytosolic tail. Internalization studies showed that the cytosolic tail of γc contains three regions located between cytosolic amino acids 1–35, 35–40, and 40–65 involved in γc endocytosis. Successive deletions of these motifs result in reduced endocytosis. One region containing the 5 cytosolic amino acids 36–40 is essential to direct γc to the degradation pathway. These sorting sequences, by participating in the fine tuning of cell surface γcexpression, might somewhat regulate the cell responsiveness to interleukins whose receptors share this component.
Footnotes
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↵* This work was supported by the CNRS “Action Biologie Cellulaire,” by the Human Science Frontier Program, and by the Ligue Nationale contre le Cancer, Comité de Paris (for support to purchase a charge-coupled device camera).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ Supported by an Assistance Publique-CNRS program.
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↵§ To whom all correspondence should be addressed: Unité de Biologie des Interactions Cellulaires, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France. Tel.: 33-1-45-68-85-74; Fax: 33-1-40-61-32-38; E-mail: adautry{at}pasteur.fr.
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↵2 E. Morelon, unpublished results.
- Abbreviations:
- IL
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interleukin
- ILR
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interleukin receptor
- PBS
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phosphate-buffered saline
- PCR
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polymerase chain reaction
- mAb(s)
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monoclonal antibody(ies)
- FITC
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fluorescein isothiocyanate.
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- Received April 2, 1998.
- Revision received June 8, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
