Inclusions of disordered protein are a characteristic feature of most neurodegenerative diseases, including Huntington's disease. Huntington's disease is caused by expansion of a polyglutamine tract in the huntingtin protein; mutant huntingtin protein (mHtt) is unstable and accumulates in large intracellular inclusions both in affected individuals and when expressed in eukaryotic cells. Using mHtt-GFP expressed in Saccharomyces cerevisiae, we find that mHtt-GFP inclusions are dynamic, mobile, gel-like structures that concentrate mHtt together with the disaggregase Hsp104. Although inclusions may associate with the vacuolar membrane, the association is reversible and we find that inclusions of mHtt in S. cerevisiae are not taken up by the vacuole or other organelles. Instead, a pulse-chase study using photoconverted mHtt-mEos2 revealed that mHtt is directly and continuously removed from the inclusion body. In addition to mobile inclusions, we also imaged and tracked the movements of small particles of mHtt-GFP and determine that they move randomly. These observations suggest that inclusions may grow through the collision and coalescence of small aggregative particles.

中文翻译：

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亨廷顿蛋白夹杂物是动态相分离的隔室。

蛋白质紊乱的包裹体是包括亨廷顿氏病在内的大多数神经退行性疾病的特征。亨廷顿舞蹈病是由亨廷顿蛋白中的聚谷氨酰胺束扩张引起的。突变亨廷顿蛋白（mHtt）不稳定，并且在受影响的个体中以及在真核细胞中表达时都积累在较大的细胞内包裹物中。使用在酿酒酵母中表达的mHtt-GFP ，我们发现mHtt-GFP包含物是动态的，可移动的，凝胶状结构，可将mHtt与Disaggregasease Hsp104集中在一起。尽管内含物可能与液泡膜相关，但这种结合是可逆的，我们发现酿酒酵母中的mHtt内含物不被液泡或其他细胞器吸收。取而代之的是，使用光转换的mHtt-mEos2进行的脉冲追踪研究表明，mHtt直接并连续地从包涵体中去除。除了移动夹杂物，我们还对mHtt-GFP小颗粒的运动进行了成像和跟踪，并确定它们是随机运动的。这些观察结果表明，夹杂物可能通过小的聚集颗粒的碰撞和聚结而生长。