Department of Biology, Institute of Molecular Microbiology, University of Konstanz, 78457 Konstanz, Germany.
Department of Biology, Applied Bioinformatics Laboratory, University of Konstanz, 78457 Konstanz, Germany.
Science. 2015 Apr 10;348(6231):201-7. doi: 10.1126/science.aaa5335.
The sorting of proteins to the appropriate compartment is one of the most fundamental cellular processes. We found that in the model organism Caenorhabditis elegans, correct cotranslational endoplasmic reticulum (ER) transport required the suppressor activity of the nascent polypeptide-associated complex (NAC). NAC did not affect the accurate targeting of ribosomes to ER translocons mediated by the signal recognition particle (SRP) pathway but inhibited additional unspecific contacts between ribosomes and translocons by blocking their autonomous binding affinity. NAC depletion shortened the life span of Caenorhabditis elegans, caused global mistargeting of translating ribosomes to the ER, and provoked incorrect import of mitochondrial proteins into the ER lumen, resulting in a strong impairment of protein homeostasis in both compartments. Thus, the antagonistic targeting activity of NAC is important in vivo to preserve the robustness and specificity of cellular protein-sorting routes.
蛋白质的分拣到适当的隔室是最基本的细胞过程之一。我们发现，在模式生物秀丽隐杆线虫中，正确的共翻译内质网（ER）运输需要新生多肽相关复合物（NAC）的抑制活性。NAC 不影响信号识别颗粒（SRP）途径介导的核糖体到 ER 易位子的准确靶向，但通过阻断它们的自主结合亲和力来抑制核糖体和易位子之间的额外非特异性接触。NAC 耗竭缩短了秀丽隐杆线虫的寿命，导致翻译核糖体在 ER 中的全局靶向错误，并引发线粒体蛋白错误地导入 ER 腔，导致两个隔室中的蛋白质平衡严重受损。因此，NAC 的拮抗靶向活性在体内对于保持细胞蛋白质分拣途径的稳健性和特异性非常重要。
