Department of Physics and Astronomy, Neuroscience Program and Quantitative Biology Institute, Ohio University, Athens, OH.
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI.
J Cell Biol. 2019 Jan 7;218(1):112-124. doi: 10.1083/jcb.201711022. Epub 2018 Nov 6.
Classic pulse-chase studies have shown that actin is conveyed in slow axonal transport, but the mechanistic basis for this movement is unknown. Recently, we reported that axonal actin was surprisingly dynamic, with focal assembly/disassembly events ("actin hotspots") and elongating polymers along the axon shaft ("actin trails"). Using a combination of live imaging, superresolution microscopy, and modeling, in this study, we explore how these dynamic structures can lead to processive transport of actin. We found relatively more actin trails elongated anterogradely as well as an overall slow, anterogradely biased flow of actin in axon shafts. Starting with first principles of monomer/filament assembly and incorporating imaging data, we generated a quantitative model simulating axonal hotspots and trails. Our simulations predict that the axonal actin dynamics indeed lead to a slow anterogradely biased flow of the population. Collectively, the data point to a surprising scenario where local assembly and biased polymerization generate the slow axonal transport of actin without involvement of microtubules (MTs) or MT-based motors. Mechanistically distinct from polymer sliding, this might be a general strategy to convey highly dynamic cytoskeletal cargoes.
经典的脉冲追踪研究表明，肌动蛋白在缓慢的轴突运输中传递，但这种运动的机制尚不清楚。最近，我们报告称，轴突中的肌动蛋白出人意料地具有动态性，存在焦点组装/拆卸事件（“肌动蛋白热点”）和沿轴突杆伸长的聚合物（“肌动蛋白痕迹”）。在这项研究中，我们结合使用活体成像、超分辨率显微镜和建模技术，探讨了这些动态结构如何导致肌动蛋白的连续运输。我们发现，相对更多的肌动蛋白痕迹向前伸长，并且轴突杆中整体呈现出缓慢的、向前倾斜的肌动蛋白流动。从单体/纤维组装的基本原理出发，并结合成像数据，我们生成了一个定量模型来模拟轴突热点和痕迹。我们的模拟预测，轴突中的肌动蛋白动力学确实导致了群体的缓慢向前倾斜流动。总的来说，这些数据表明了一个令人惊讶的情况，即局部组装和偏向聚合产生了肌动蛋白的缓慢轴突运输，而不涉及微管（MTs）或基于 MT 的马达。与聚合物滑动在机制上不同，这可能是一种普遍的策略，可以传递高度动态的细胞骨架货物。
