Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO, 80523, USA.
Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, 02118, USA.
Nat Commun. 2019 Aug 9;10(1):3614. doi: 10.1038/s41467-019-11550-w.
Stress granules are membraneless protein- and mRNA-rich organelles that form in response to perturbations in environmental conditions. Stress granule formation is reversible, and persistent stress granules have been implicated in a variety of neurodegenerative disorders, including amyotrophic lateral sclerosis. However, characterization of the factors involved in dissolving stress granules is incomplete. Many stress granule proteins contain prion-like domains (PrLDs), some of which have been linked to stress granule formation. Here, we demonstrate that the PrLD-containing yeast protein kinase Sky1 is a stress granule component. Sky1 is recruited to stress granules in part via its PrLD, and Sky1's kinase activity regulates timely stress granule disassembly during stress recovery. This effect is mediated by phosphorylation of the stress granule component Npl3. Sky1 can compensate for defects in chaperone-mediated stress granule disassembly and vice-versa, demonstrating that cells have multiple overlapping mechanisms for re-solubilizing stress granule components.
应激颗粒是一种无膜的富含蛋白质和 mRNA 的细胞器，它在环境条件发生变化时形成。应激颗粒的形成是可逆的，持久的应激颗粒与多种神经退行性疾病有关，包括肌萎缩侧索硬化症。然而，参与溶解应激颗粒的因素的特征描述并不完整。许多应激颗粒蛋白含有朊病毒样结构域（PrLDs），其中一些与应激颗粒的形成有关。在这里，我们证明含有 PrLD 的酵母蛋白激酶 Sky1 是应激颗粒的组成部分。Sky1 通过其 PrLD 部分被募集到应激颗粒中，并且 Sky1 的激酶活性调节应激恢复过程中应激颗粒的适时解体。这种效应是通过应激颗粒成分 Npl3 的磷酸化介导的。Sky1 可以补偿伴侣介导的应激颗粒解体缺陷，反之亦然，这表明细胞具有多种重叠的机制来重新溶解应激颗粒成分。
