Multivalent Proteins Rapidly and Reversibly Phase-Separate upon Osmotic Cell Volume Change.
Multivalent Proteins Rapidly and Reversibly Phase-Separate upon Osmotic Cell Volume Change.
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DOI：
10.1016/j.molcel.2020.08.004
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发表时间：
2020-09-17
期刊：
影响因子：
16
通讯作者：
Walter NG
中科院分区：
文献类型：
--
作者：
Jalihal AP;Pitchiaya S;Xiao L;Bawa P;Jiang X;Bedi K;Parolia A;Cieslik M;Ljungman M;Chinnaiyan AM;Walter NG
处理体(PB)和应激颗粒(SG)是分别在生理和应激条件下观察到的亚细胞、无膜室的突出例子。我们观察到，在哺乳动物细胞中，三聚体PB蛋白DCP1a在高渗应激时迅速(在~10 S范围内)相分离，在等渗抢救时(在~100 S以上)溶解，即使在多次渗透扰动后，对细胞活力的影响也很小。值得注意的是，这种快速的细胞内高渗相分离(HOP)与细胞体积压缩的程度有关，与SG组装不同，并且广泛地表现在几种细胞类型的同源多聚体(价态≥2)蛋白中。值得注意的是，啤酒花隔离了活跃转录的基因组位点中的前mRNA切割因子组分，为高渗透压诱导转录终止的整体损害提供了一种机制。总之，我们的数据表明，多聚体蛋白质组对水合作用和分子拥挤的变化做出快速反应，揭示了一种意想不到的全球编程相分离和隔离模式。细胞不断地经历渗透变化。这些外部变化导致细胞体积的变化，从而导致分子拥挤的内部状态。这里，Jalihal和Pitchiaya等人。表明多聚体蛋白质通过经历快速和可逆的相分离来对这种细胞变化做出快速反应。
Processing bodies (PB) and stress granules (SG) are prominent examples of sub-cellular, membrane-less compartments that are observed under physiological and stress conditions, respectively. We observe that the trimeric PB protein DCP1A rapidly (within ~10 s) phase-separates in mammalian cells during hyperosmotic stress and dissolves upon isosmotic rescue (over ~100 s) with minimal impact on cell viability even after multiple cycles of osmotic perturbation. Strikingly, this rapid intracellular hyperosmotic phase separation (HOPS) correlates with the degree of cell volume compression, distinct from SG assembly, and is exhibited broadly by homo-multimeric (valency ≥ 2) proteins across several cell types. Notably, HOPS sequesters pre-mRNA cleavage factor components from actively transcribing genomic loci, providing a mechanism for hyperosmolarity-induced global impairment of transcription termination. Together, our data suggest that the multimeric proteome rapidly responds to changes in hydration and molecular crowding, revealing an unexpected mode of globally programmed phase separation and sequestration. Cells constantly experience osmotic variation. These external changes lead to changes in cell volume, and consequently the internal state of molecular crowding. Here, Jalihal and Pitchiaya et al. show that multimeric proteins respond rapidly to such cellular changes by undergoing rapid and reversible phase separation.
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