How a cytokine is chaperoned through the secretory pathway by complexing with its own receptor

Lessons from interleukin-15 (IL-15)/IL-15 receptor

Erwin H. Duitman, Zane Orinska, Elena Bulanova, Ralf Paus, Silvia Bulfone-Paus

Research output: Contribution to journalArticle

49 Citations (Scopus)

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

Original languageEnglish (US)
Pages (from-to)4851-4861
Number of pages11
JournalMolecular and Cellular Biology
Volume28
Issue number15
DOIs
StatePublished - Aug 1 2008
Externally publishedYes

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Interleukin-15 Receptors
Interleukin-15
Secretory Pathway
Cytokines
Cytokine Receptors
Endoplasmic Reticulum
Ligands
Golgi Apparatus

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

How a cytokine is chaperoned through the secretory pathway by complexing with its own receptor : Lessons from interleukin-15 (IL-15)/IL-15 receptor. / Duitman, Erwin H.; Orinska, Zane; Bulanova, Elena; Paus, Ralf; Bulfone-Paus, Silvia.

In: Molecular and Cellular Biology, Vol. 28, No. 15, 01.08.2008, p. 4851-4861.

Research output: Contribution to journalArticle

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