The processes underlying formation and growth of unfolded protein inclusions are relevant to neurodegenerative diseases. In S. cerevisiae, inclusion bodies formed by mutant huntingtin have characteristics of phase-separated compartments: they are mobile, ovoid, and the contents are diffusible. We have used molecular genetics and quantitative confocal microscopy to probe the relationship between concentration and inclusion growth in vivo. Our analysis and modeling of the growth of mutant huntingtin inclusion bodies (mHtt IBs) suggests that there is a cytoplasmic threshold concentration that triggers the formation of an IB, regardless of proteasome capacity, and that reduction in cytoplasmic mHtt causes IBs to shrink. These findings confirm that the IB is a phase-separated compartment that continuously exchanges material with the cytoplasm. The growth rate of the IB is most consistent with a model in which material is incorporated through collision with the IB. A small remnant of the IB is relatively long-lasting, suggesting that the IB contains a core that is structurally distinct, and which may serve to nucleate it.

中文翻译：

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阈值浓度和随机碰撞决定了稳定核中相分离亨廷顿蛋白包合物的生长

未折叠蛋白内含物形成和生长的过程与神经退行性疾病有关。在酿酒酵母中，由突变亨廷顿蛋白形成的包涵体具有相分离隔室的特征：它们是可移动的，卵形的，并且内容物是可扩散的。我们已经使用分子遗传学和定量共聚焦显微镜来探究体内浓度与内含物生长之间的关系。我们对突变型亨廷顿蛋白包涵体（mHtt IBs）生长的分析和建模表明，无论蛋白酶体能力如何，都有细胞质阈值浓度会触发IB的形成，并且细胞质mHtt的降低会导致IBs缩小。这些发现证实IB是相分离的区室，其与细胞质连续交换物质。IB的增长率与通过与IB碰撞合并材料的模型最一致。IB的一小部分残余物相对较持久，这表明IB包含结构上不同的核，可用来使其成核。