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An apparent core/shell architecture of polyQ aggregates in the aging Caenorhabditis elegans neuron
Protein Science ( IF 8 ) Pub Date : 2021-05-09 , DOI: 10.1002/pro.4105
Rachel S Fisher 1 , Rosa Meyo Jimenez 1 , Elizabeth Soto 1 , Darin Kalev 1 , Shana Elbaum-Garfinkle 1, 2
Affiliation  

Huntington's disease is caused by a polyglutamine (polyQ) expansion in the huntingtin protein which results in its abnormal aggregation in the nervous system. Huntingtin aggregates are linked to toxicity and neuronal dysfunction, but a comprehensive understanding of the aggregation mechanism in vivo remains elusive. Here, we examine the morphology of polyQ aggregates in Caenorhabditis elegans mechanosensory neurons as a function of age using confocal and fluorescence lifetime imaging microscopy. We find that aggregates in young worms are mostly spherical with homogenous intensity, but as the worm ages aggregates become substantially more heterogeneous. Most prominently, in older worms we observe an apparent core/shell morphology of polyQ assemblies with decreased intensity in the center. The fluorescence lifetime of polyQ is uniform across the aggregate indicating that the dimmed intensity in the assembly center is most likely not due to quenching or changes in local environment, but rather to displacement of fluorescent polyQ from the central region. This apparent core/shell architecture of polyQ aggregates in aging C. elegans neurons contributes to the diverse landscape of polyQ aggregation states implicated in Huntington's disease.

中文翻译:

衰老的秀丽隐杆线虫神经元中 polyQ 聚集体的明显核/壳结构

亨廷顿氏病是由亨廷顿蛋白中的多聚谷氨酰胺 (polyQ) 扩增导致其在神经系统中的异常聚集引起的。亨廷顿蛋白聚集体与毒性和神经元功能障碍有关,但对体内聚集机制的全面了解仍然难以捉摸。在这里,我们检查了秀丽隐杆线虫中 polyQ 聚集体的形态使用共聚焦和荧光寿命成像显微镜作为年龄函数的机械感觉神经元。我们发现年轻蠕虫中的聚集体大多是具有均匀强度的球形,但随着蠕虫年龄的增长,聚集体变得更加异质。最突出的是,在较老的蠕虫中,我们观察到 polyQ 组件的明显核/壳形态,中心强度降低。polyQ 的荧光寿命在整个聚合体中是均匀的,表明组装中心的暗淡强度很可能不是由于淬火或局部环境的变化,而是由于荧光 polyQ 从中心区域的位移。这种明显的 polyQ 聚集体在老化C. elegans中的核/壳结构神经元有助于与亨廷顿病有关的 polyQ 聚集状态的多样性。
更新日期:2021-06-13
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