This Article Full Text Full Text (PDF) Other Versions of this Article: MCB.02178-07v1 28/15/4851    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Duitman, E. H. Articles by Bulfone-Paus, S. PubMed PubMed Citation Articles by Duitman, E. H. Articles by Bulfone-Paus, S.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, August 2008, p. 4851-4861, Vol. 28, No. 15
0270-7306/08/$08.00+0     doi:10.1128/MCB.02178-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

How a Cytokine Is Chaperoned through the Secretory Pathway by Complexing with Its Own Receptor: Lessons from Interleukin-15 (IL-15)/IL-15 Receptor

Department of Immunology and Cell Biology, Research Centre Borstel, D-23845 Borstel, Germany,¹ Department of Dermatology, University Hospital Schleswig-Holstein, Campus Lübeck, University of Lübeck, D-23538 Lübeck, Germany²

Received 9 December 2007/ Returned for modification 16 February 2008/ Accepted 19 May 2008

While it is well appreciated that receptors for secreted cytokines transmit ligand-induced signals, little is known about additional roles for cytokine receptor components in the control of ligand transport and secretion. Here, we show that interleukin-15 (IL-15) translocation into the endoplasmic reticulum occurs independently of the presence of IL-15 receptor (IL-15R). Subsequently, however, IL-15 is transported through the Golgi apparatus only in association with IL-15R and then is secreted. This intracellular IL-15/IL-15R complex already is formed in the endoplasmic reticulum and, thus, enables the further trafficking of complexed IL-15 through the secretory pathway. Just transfecting IL-15R in cells, which transcribe but normally do not secrete IL-15, suffices to induce IL-15 secretion. Thus, we provide the first evidence of how a cytokine is chaperoned through the secretory pathway by complexing with its own high-affinity receptor and show that IL-15/IL-15R offers an excellent model system for the further exploration of this novel mechanism for the control of cytokine secretion.

Published ahead of print on 27 May 2008.