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

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2008 May 29

PMID 18505820

Citations 36

Authors

Erwin H Duitman

Zane Orinska

Elena Bulanova

Ralf Paus

Silvia Bulfone-Paus

Affiliations

Soon will be listed here.

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.

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