Stochastic simulation of neurofilament transport in axons: The "stop-and-go" hypothesis
Stochastic simulation of neurofilament transport in axons: The "stop-and-go" hypothesis
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DOI：
10.1091/mbc.e05-02-0141
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发表时间：
2005-09-01
影响因子：
3.3
通讯作者：
Jung, P
中科院分区：
文献类型：
--
作者：
Brown, A;Wang, L;Jung, P
根据慢速轴突运输的“走走停停”假说，细胞骨架和胞质蛋白沿着轴突以很快的速度运输，但平均速度很慢，因为运动不频繁且是双向的。为了测试这一假设是否可以解释体内缓慢轴突运输的动力学，我们开发了轴突中神经丝运输的随机模型。我们提出，神经丝沿着细胞骨架轨道沿顺行和逆行方向移动，在短暂的快速移动和短暂的“在轨”暂停之间交替，并且它们也可以暂时脱离这些轨道，导致更长时间的“偏离轨道”暂停。我们通过对培养神经元轴突中单个神经丝的移动和暂停行为的详细分析，得出了模型的动力学参数。我们证明该模型可以匹配通过体内放射性同位素脉冲标记获得的神经丝传输波的形状、速度和传播。该模型预测，轴突神经丝在沿着轴突的旅程中花费大约 8% 的时间在正轨上，并花费大约 97% 的时间暂停。
According to the "stop-and-go" hypothesis of slow axonal transport, cytoskeletal and cytosolic proteins are transported along axons at fast rates but the average velocity is slow because the movements are infrequent and bidirectional. To test whether this hypothesis can explain the kinetics of slow axonal transport in vivo, we have developed a stochastic model of neurofilament transport in axons. We propose that neurofilaments move in both anterograde and retrograde directions along cytoskeletal tracks, alternating between short bouts of rapid movement and short "on-track" pauses, and that they can also temporarily disengage from these tracks, resulting in more prolonged "off-track" pauses. We derive the kinetic parameters of the model from a detailed analysis of the moving and pausing behavior of single neurofilaments in axons of cultured neurons. We show that the model can match the shape, velocity, and spreading of the neurofilament transport waves obtained by radioisotopic pulse labeling in vivo. The model predicts that axonal neurofilaments spend similar to 8% of their time on track and similar to 97% of their time pausing during their journey along the axon.