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 language | English (US) |
|---|---|
| Pages (from-to) | 4851-4861 |
| Number of pages | 11 |
| Journal | Molecular and Cellular Biology |
| Volume | 28 |
| Issue number | 15 |
| DOIs | |
| State | Published - Aug 1 2008 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - How a cytokine is chaperoned through the secretory pathway by complexing with its own receptor
T2 - Lessons from interleukin-15 (IL-15)/IL-15 receptor
AU - Duitman, Erwin H.
AU - Orinska, Zane
AU - Bulanova, Elena
AU - Paus, Ralf
AU - Bulfone-Paus, Silvia
PY - 2008/8/1
Y1 - 2008/8/1
N2 - 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.
AB - 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.
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U2 - 10.1128/MCB.02178-07
DO - 10.1128/MCB.02178-07
M3 - Article
VL - 28
SP - 4851
EP - 4861
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
IS - 15
ER -