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Mol. Cell. Biol. 28 (15): 4851-4861

Copyright © 2008 by the 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 {alpha}{triangledown}

Erwin H. Duitman,1 Zane Orinska,1 Elena Bulanova,1 Ralf Paus,2, and Silvia Bulfone-Paus1*

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 for publication 9 December 2007. Revision received 16 February 2008. Accepted for publication 19 May 2008.

Abstract: 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 {alpha} (IL-15R{alpha}). Subsequently, however, IL-15 is transported through the Golgi apparatus only in association with IL-15R{alpha} and then is secreted. This intracellular IL-15/IL-15R{alpha} 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{alpha} 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{alpha} offers an excellent model system for the further exploration of this novel mechanism for the control of cytokine secretion.


* Corresponding author. Mailing address: Department of Immunology and Cell Biology, Research Center Borstel, Parkallee 22, D-23845 Borstel, Germany. Phone: 49 4537 188200. Fax: 49 4537 188403. E-mail: sbulfone{at}fz-borstel.de

{triangledown} Published ahead of print on 27 May 2008.



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