A deep proteomics perspective on CRM1-mediated nuclear export and nucleocytoplasmic partitioning
A deep proteomics perspective on CRM1-mediated nuclear export and nucleocytoplasmic partitioning
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DOI：
10.7554/elife.11466
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发表时间：
2015-12-17
期刊：
影响因子：
7.7
通讯作者：
Goerlich, Dirk
中科院分区：
文献类型：
--
作者：
Kirli, Koray;Karaca, Samir;Goerlich, Dirk
CRM1是一种高度保守的RanGTP酶驱动的输出蛋白，将蛋白质和RNP从细胞核运送到细胞质。我们现在深入探索了CRM 1的货物谱，并鉴定了令人惊讶的大量底物，即来自酵母S的>700种输出底物。酿酒酵母，非洲爪蟾卵母细胞中约为1000，人细胞中>1050。此外，我们量化了非洲爪蟾卵母细胞的细胞核和细胞质之间的约5000个独特的蛋白质的分区。这些数据表明，新的CRM1功能的空间控制囊泡外套组装，中心体，自噬，过氧化物酶体生物合成，细胞骨架，核糖体成熟，翻译，mRNA降解，更一般地在排除一个潜在的有害作用的细胞质内的细胞核内部的途径。也有许多新的情况下，CRM1似乎在监管电路中发挥作用.总而言之，我们的数据集允许前所未有的见解核质组织的真核细胞，到一个非常混杂的输出的贡献，它提供了一个新的基础内斯预测。
CRM1 is a highly conserved, RanGTPase-driven exportin that carries proteins and RNPs from the nucleus to the cytoplasm. We now explored the cargo-spectrum of CRM1 in depth and identified surprisingly large numbers, namely >700 export substrates from the yeast S. cerevisiae, approximate to 1000 from Xenopus oocytes and >1050 from human cells. In addition, we quantified the partitioning of approximate to 5000 unique proteins between nucleus and cytoplasm of Xenopus oocytes. The data suggest new CRM1 functions in spatial control of vesicle coat-assembly, centrosomes, autophagy, peroxisome biogenesis, cytoskeleton, ribosome maturation, translation, mRNA degradation, and more generally in precluding a potentially detrimental action of cytoplasmic pathways within the nuclear interior. There are also numerous new instances where CRM1 appears to act in regulatory circuits. Altogether, our dataset allows unprecedented insights into the nucleocytoplasmic organisation of eukaryotic cells, into the contributions of an exceedingly promiscuous exportin and it provides a new basis for NES prediction.