How a cytokine is chaperoned through the secretory pathway by complexing with its own receptor:: Lessons from interleukin-15 (IL-15)/IL-15 receptor α
How a cytokine is chaperoned through the secretory pathway by complexing with its own receptor:: Lessons from interleukin-15 (IL-15)/IL-15 receptor α
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DOI：
10.1128/mcb.02178-07
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发表时间：
2008-08-01
影响因子：
5.3
通讯作者：
Bulfone-Paus, Silvia
中科院分区：
文献类型：
--
作者：
Duitman, Erwin H.;Orinska, Zane;Bulfone-Paus, Silvia
虽然很好地理解，分泌的细胞因子的受体传递配体诱导的信号，很少有人知道细胞因子受体成分在控制配体转运和分泌的其他作用。在这里，我们表明，白细胞介素-15（IL-15）易位到内质网发生独立的IL-15受体α（IL-15 R α）的存在。然而，随后，IL-15仅与IL-15 R α结合转运通过高尔基体，然后分泌。这种细胞内IL-15/IL-15 R α。复合物已经在内质网中形成，因此，能够通过分泌途径进一步运输复合的IL-15。仅在转录但通常不分泌IL-15的细胞中抑制IL-15 R α就足以诱导IL-15分泌。因此，我们提供了第一个证据，细胞因子是如何通过分泌途径与自己的高亲和力受体复合伴侣，并表明IL-15/IL-15 R α提供了一个很好的模型系统，为进一步探索这种新的机制，控制细胞因子分泌。
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.