Stress granules and cell signaling: more than just a passing phase?

Stress granules and cell signaling: more than just a passing phase?
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DOI:
10.1016/j.tibs.2013.07.004
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发表时间:
2013-10
影响因子:
13.8
通讯作者:
Anderson, Paul
Anderson, Paul
中科院分区:
生物学1区
文献类型:
--
作者:
Kedersha, Nancy;Ivanov, Pavel;Anderson, Paul

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应激颗粒(Stress granules,SG)含有抑制性停滞的mRNA、相关的前起始因子和特异的RNA结合蛋白。此外,许多信号蛋白被招募到SGs和/或影响它们的组装,这是短暂的,仅持续到细胞适应压力或死亡。除了作为mRNA分流中心的作用外,我们认为SG构成了类似于经典多蛋白信号结构域(如跨膜受体复合物)的RNA中心信号枢纽。作为信号中心,SG的形成传达了一种“紧急状态”,它们的短暂存在通过拦截和隔离信号成分改变了多种信号通路。SG组装和下游信号传导功能可能需要由RNA结合和信号传导蛋白共享的固有无序的、易于聚集的蛋白质区域促进的胞质相变。
Stress granules (SGs) contain translationally-stalled mRNAs, associated preinitiation factors and specific RNA-binding proteins. In addition, many signaling proteins are recruited to SGs and/or influence their assembly, which is transient, lasting only until the cells adapt to stress or die. Beyond their role as mRNA triage centers, we posit that SGs constitute RNA-centric signaling hubs analogous to classical multiprotein signaling domains such as transmembrane receptor complexes. As signaling centers, SG formation communicates a “state of emergency”, and their transient existence alters multiple signaling pathways by intercepting and sequestering signaling components. SG assembly and downstream signaling functions may require a cytosolic phase transition facilitated by intrinsically disordered, aggregation-prone protein regions shared by RNA-binding and signaling proteins.
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