Local Acceleration of Neurofilament Transport at Nodes of Ranvier
Local Acceleration of Neurofilament Transport at Nodes of Ranvier
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Ranvier 节点神经丝传输的局部加速
DOI：
10.1523/jneurosci.2272-18.2018
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发表时间：
2018-12
影响因子：
5.3
通讯作者：
Anthony Brown
中科院分区：
文献类型：
--
作者：
Cynthia L. Walker;Atsuko Uchida;Yinyun Li;Niraj Trivedi;J. Daniel Fenn;Paula C. Monsma;Roxanne C. Lariviére;Jean-Pierre Julien;Peter Jung;Anthony Brown
有髓轴突在朗飞节处收缩。这些收缩在生理上很重要，因为它们增加了跳跃神经传导的速度，但它们也代表了轴突运输货物运动的潜在瓶颈。一种货物是神经丝，它们是丰富的充满空间的细胞骨架聚合物，具有增加轴突口径的作用。神经丝沿着轴突双向移动，在快速运动和长时间停顿之间交替。引人注目的是，节点处的轴突收缩伴随着神经丝数量的减少，在最大的轴突中，神经丝数量可能减少 10 倍。为了研究神经丝如何引导这些收缩，我们开发了一种转基因小鼠品系，它在神经元中表达可光激活的荧光神经丝蛋白。我们使用脉冲逃逸荧光光激活技术来分析该品系的雄性和雌性小鼠的胫神经成熟有髓轴突中的神经丝运输。荧光神经丝在节点中比在侧翼节间更快地离开激活区域，表明神经丝在节点中的运输更快。通过计算模型，我们表明这种节点加速很大程度上可以通过神经丝运输占空比（即神经丝移动时间的比例）的局部增加来解释。我们认为这种瞬态加速的作用是维持跨节点收缩的恒定神经丝通量，就像河岸变窄时电流增加一样。通过这种方式，可以防止神经丝在侧翼节间堆积，确保这些生理上重要的轴突域稳定的神经丝分布和均匀的轴突形态。意义陈述 有髓鞘轴突在朗飞结处收缩，导致神经丝数量局部显着减少。这些收缩在生理上很重要，因为它们提高了跳跃神经传导的效率，但它们也代表了神经丝的轴突运输的潜在瓶颈，神经丝沿着轴突以快速间歇的方式移动。对成熟有髓轴突中神经丝运输的离体成像表明，神经丝聚合物通过瞬时加速来导航这些节点轴突收缩，就像河岸变窄时水流增加一样。这种局部加速对于确保跨节点收缩的稳定轴突形态是必要的，这可能解释了朗飞节点在神经毒性神经病和神经退行性疾病动物模型中对神经丝积累的脆弱性。
Myelinated axons are constricted at nodes of Ranvier. These constrictions are important physiologically because they increase the speed of saltatory nerve conduction, but they also represent potential bottlenecks for the movement of axonally transported cargoes. One type of cargo are neurofilaments, which are abundant space-filling cytoskeletal polymers that function to increase axon caliber. Neurofilaments move bidirectionally along axons, alternating between rapid movements and prolonged pauses. Strikingly, axon constriction at nodes is accompanied by a reduction in neurofilament number that can be as much as 10-fold in the largest axons. To investigate how neurofilaments navigate these constrictions, we developed a transgenic mouse strain that expresses a photoactivatable fluorescent neurofilament protein in neurons. We used the pulse-escape fluorescence photoactivation technique to analyze neurofilament transport in mature myelinated axons of tibial nerves from male and female mice of this strain ex vivo. Fluorescent neurofilaments departed the activated region more rapidly in nodes than in flanking internodes, indicating that neurofilament transport is faster in nodes. By computational modeling, we showed that this nodal acceleration can be explained largely by a local increase in the duty cycle of neurofilament transport (i.e., the proportion of the time that the neurofilaments spend moving). We propose that this transient acceleration functions to maintain a constant neurofilament flux across nodal constrictions, much as the current increases where a river narrows its banks. In this way, neurofilaments are prevented from piling up in the flanking internodes, ensuring a stable neurofilament distribution and uniform axonal morphology across these physiologically important axonal domains. SIGNIFICANCE STATEMENT Myelinated axons are constricted at nodes of Ranvier, resulting in a marked local decrease in neurofilament number. These constrictions are important physiologically because they increase the efficiency of saltatory nerve conduction, but they also represent potential bottlenecks for the axonal transport of neurofilaments, which move along axons in a rapid intermittent manner. Imaging of neurofilament transport in mature myelinated axons ex vivo reveals that neurofilament polymers navigate these nodal axonal constrictions by accelerating transiently, much as the current increases where a river narrows its banks. This local acceleration is necessary to ensure a stable axonal morphology across nodal constrictions, which may explain the vulnerability of nodes of Ranvier to neurofilament accumulations in animal models of neurotoxic neuropathies and neurodegenerative diseases.
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DOI：
10.1083/jcb.200303138
发表时间：
2003-05-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ackerley S;Thornhill P;Grierson AJ;Brownlees J;Anderton BH;Leigh PN;Shaw CE;Miller CC
通讯作者：
Miller CC
DOI：
10.1083/jcb.151.5.1013
发表时间：
2000-11-27
期刊：
The Journal of cell biology
影响因子：
--
作者：
Sánchez I;Hassinger L;Sihag RK;Cleveland DW;Mohan P;Nixon RA
通讯作者：
Nixon RA
DOI：
10.1523/jneurosci.3829-08.2009
发表时间：
2009-05-20
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Alami NH;Jung P;Brown A
通讯作者：
Brown A
DOI：
10.1083/jcb.126.4.1031
发表时间：
1994-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Nixon RA;Paskevich PA;Sihag RK;Thayer CY
通讯作者：
Thayer CY
DOI：
10.1016/b978-0-12-775230-3.50014-5
发表时间：
1984
期刊：
--
影响因子：
--
作者：
J. Jacobs
通讯作者：
J. Jacobs