Autophagy-based unconventional secretory pathway for extracellular delivery of IL-1β
Autophagy-based unconventional secretory pathway for extracellular delivery of IL-1β
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DOI：
10.1038/emboj.2011.398
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发表时间：
2011-11-30
期刊：
影响因子：
11.4
通讯作者：
Deretic, Vojo
中科院分区：
文献类型：
--
作者：
Dupont, Nicolas;Jiang, Shanya;Deretic, Vojo
自噬控制真核细胞质的质量和数量，同时执行两个进化上高度保守的功能：在饥饿期间通过胞质溶胶自消化的细胞自主提供能量和营养物质，以及去除失效的细胞器和超过其他细胞降解系统能力的大聚集体。与这些自我消化过程相反，酵母中的自噬具有额外的生物合成功能。然而，在哺乳动物中没有描述过自噬的等效生物合成作用。在这里，我们表明，在哺乳动物细胞中，自噬具有迄今为止未得到赞赏的积极贡献的生物合成和分泌的促炎细胞因子IL-1 β通过出口途径，依赖于Atg 5，炎性小体，至少一个的两个哺乳动物高尔基体重组堆积蛋白（GRASP）旁系同源物，GRASP 55（GORASP 2）和Rab 8a。这一过程是一种非常规的分泌，它将自噬的功能表现扩展到了哺乳动物的自我消化和质量控制作用之外。它使一个缺乏信号肽序列的胞质蛋白亚组，因此无法通过ER进入常规途径，进入基于自噬的分泌途径，促进它们从细胞质中退出。The EMBO Journal（2011）30，4701-4711. doi：10.1038/daj.2011.398; 2011年11月8日在线发布
Autophagy controls the quality and quantity of the eukaryotic cytoplasm while performing two evolutionarily highly conserved functions: cell-autonomous provision of energy and nutrients by cytosol autodigestion during starvation, and removal of defunct organelles and large aggregates exceeding the capacity of other cellular degradative systems. In contrast to these autodigestive processes, autophagy in yeast has additional, biogenesis functions. However, no equivalent biosynthetic roles have been described for autophagy in mammals. Here, we show that in mammalian cells, autophagy has a hitherto unappreciated positive contribution to the biogenesis and secretion of the proinflammatory cytokine IL-1 beta via an export pathway that depends on Atg5, inflammasome, at least one of the two mammalian Golgi reassembly stacking protein (GRASP) paralogues, GRASP55 (GORASP2) and Rab8a. This process, which is a type of unconventional secretion, expands the functional manifestations of autophagy beyond autodigestive and quality control roles in mammals. It enables a subset of cytosolic proteins devoid of signal peptide sequences, and thus unable to access the conventional pathway through the ER, to enter an autophagy-based secretory pathway facilitating their exit from the cytoplasm. The EMBO Journal (2011) 30, 4701-4711. doi:10.1038/emboj.2011.398; Published online 8 November 2011