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A critical reevaluation of the stationary axonal cytoskeleton hypothesis

机译：固定轴突细胞骨架假说的关键重新评估。

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Neurofilaments are transported along axons in a rapid intermittent and bidirectional manner but there is a long-standing controversy about whether this applies to all axonal neurofilaments. Some have proposed that only a small proportion of axonal neurofilaments are mobile and that most are deposited into a persistently stationary and extensively cross-linked cytoskeleton that remains fixed in place for many months without movement, turning over very slowly. In contrast, others have proposed that this hypothesis is based on a misinterpretation of the experimental data and that, in fact, all axonal neurofilaments move. These contrary perspectives have distinct implications for our understanding of how neurofilaments are organized and reorganized in axons both in health and disease. Here, we discuss the history and substance of this controversy. We show that the published data on the kinetics and distribution of neurofilaments along axons favor a simple "stop and go" transport model in which axons contain a single population of neurofilaments that all move in a stochastic, bidirectional and intermittent manner. Based on these considerations, we propose a dynamic view of the neuronal cytoskeleton in which all neurofilaments cycle repeatedly between moving and pausing states throughout their journey along the axon. The filaments move infrequently, but the average pause duration is on the order of hours rather than weeks or months. Against this fluid backdrop, the action of molecular motors on neurofilaments can have dramatic effects on neurofilament organization that would not be possible if the neurofilaments were extensively cross-linked into a truly stationary network.
机译：神经丝以快速的断续和双向方式沿着轴突运输，但是关于这是否适用于所有轴突神经丝一直存在争议。一些人提出，只有一小部分的轴突神经丝是可移动的，并且大多数沉积在一个永久固定的，广泛交联的细胞骨架中，该骨架在没有运动的情况下可以固定好许​​多个月，翻转非常缓慢。相反，其他人则提出该假设是基于对实验数据的错误理解，并且实际上所有轴突神经丝都在运动。这些相反的观点对于我们对神经丝在健康和疾病中如何在轴突中组织和重组的理解具有不同的含义。在这里，我们讨论该争议的历史和实质。我们显示有关沿轴突的神经丝的动力学和分布的已公开数据支持简单的“停走”运输模型，其中轴突包含单个以随机，双向和间歇方式移动的神经丝群体。基于这些考虑，我们提出了神经元细胞骨架的动态视图，其中所有神经丝在沿着轴突的整个移动过程中都在运动状态和暂停状态之间反复循环。细丝很少移动，但平均停顿持续时间为数小时而不是数周或数月。在这种流体的背景下，分子运动对神经丝的作用可能会对神经丝的组织产生巨大影响，而如果神​​经丝被广泛交联成一个真正的固定网络则是不可能的。

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