Department of Pathology, University of California, San Diego, California 92093, USA.
Cytoskeleton (Hoboken). 2012 Jul;69(7):506-13. doi: 10.1002/cm.21019. Epub 2012 Mar 2.
Slow axonal transport conveys perikaryally-synthesized cytosolic proteins in a rate-class called Slow Component-b (SCb). One such protein--α-synuclein--is largely conveyed in SCb, and is also a key player in a group of neurodegenerative diseases called synucleinopathies. Axonal transport defects of α-synuclein have been hypothesized to play a role in synucleinopathies, but mechanisms moving α-synuclein in slow axonal transport are unclear. Here we use a recently developed model-system in our laboratory to visualize the slow transport of α-synuclein, comparing it to another SCb protein synapsin. Despite differences inbiological properties and overall-solubility in axons, the anterograde transport of both SCb proteins was strikingly similar, suggesting commonalities in slow axonal transport mechanisms of seemingly diverse cytosolic cargoes. The data support a model where SCb proteins dynamically organize into 'transport-competent' complexes that are conveyed via transient associations with other persistently-moving cargoes ("mobile-units"). The identity of the latter is yet unknown. Visualizing normal α-synuclein transport may also open the door to studies of α-synuclein transport in pathologic states.
缓慢轴突运输以一种称为“慢组分-b（Slow Component-b，SCb）”的速率类别来传递核周合成的细胞质蛋白。一种这样的蛋白质——α-突触核蛋白——主要在 SCb 中传递，也是一组称为突触核蛋白病的神经退行性疾病的关键参与者。α-突触核蛋白的轴突运输缺陷被假设在突触核蛋白病中发挥作用，但将 α-突触核蛋白在缓慢轴突运输中的移动机制尚不清楚。在这里，我们使用实验室最近开发的模型系统来可视化α-突触核蛋白的缓慢运输，将其与另一种 SCb 蛋白突触素进行比较。尽管在生物学特性和整体在轴突中的溶解度方面存在差异，但两种 SCb 蛋白的顺行运输非常相似，这表明看似不同的细胞质货物的缓慢轴突运输机制存在共性。该数据支持这样一种模型，即 SCb 蛋白动态地组织成“具有运输能力”的复合物，通过与其他持续移动的货物（“移动单元”）的短暂关联来传递。后者的身份尚不清楚。可视化正常的α-突触核蛋白运输也可能为研究病理状态下的α-突触核蛋白运输打开大门。
