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.

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.

journal_name

Mol Cell Biol

authors

Duitman EH,Orinska Z,Bulanova E,Paus R,Bulfone-Paus S

doi

10.1128/MCB.02178-07

subject

Has Abstract

pub_date

2008-08-01 00:00:00

pages

4851-61

issue

15

eissn

0270-7306

issn

1098-5549

pii

MCB.02178-07

journal_volume

28

pub_type

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