McMaster Centre for Advanced Light Microscopy (CALM) McMaster University, Hamilton, Canada.
Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada.
J Huntingtons Dis. 2022;11(3):269-280. doi: 10.3233/JHD-220536.
Huntingtin is a 3144 amino acid protein defined as a scaffold protein with many intracellular locations that suggest functions in these compartments. Expansion of the CAG DNA tract in the huntingtin first exon is the cause of Huntington's disease. An important tool in understanding the biological functions of huntingtin is molecular imaging at the single-cell level by microscopy and nanoscopy. The evolution of these technologies has accelerated since the Nobel Prize in Chemistry was awarded in 2014 for super-resolution nanoscopy. We are in a new era of light imaging at the single-cell level, not just for protein location, but also for protein conformation and biochemical function. Large-scale microscopy-based screening is also being accelerated by a coincident development of machine-based learning that offers a framework for truly unbiased data acquisition and analysis at very large scales. This review will summarize the newest technologies in light, electron, and atomic force microscopy in the context of unique challenges with huntingtin cell biology and biochemistry.
亨廷顿蛋白是一种由 3144 个氨基酸组成的蛋白质，被定义为一种支架蛋白，有许多细胞内位置，提示其在这些隔室中的功能。亨廷顿病的病因是亨廷顿第一外显子中 CAG DNA 片段的扩展。分子成像技术是理解亨廷顿蛋白生物学功能的重要工具，可通过显微镜和纳米镜在单细胞水平上进行。自 2014 年诺贝尔化学奖授予超分辨率纳米镜以来，这些技术的发展速度加快了。我们正处在单细胞水平的光成像新时代，不仅可以用于蛋白质定位，还可以用于蛋白质构象和生化功能。基于显微镜的大规模筛选也在加速发展，因为机器学习的出现为在非常大的范围内进行真正无偏的数据采集和分析提供了框架。本综述将总结光、电子和原子力显微镜的最新技术，这些技术与亨廷顿细胞生物学和生物化学的独特挑战有关。
