Transport of neurofilaments in growing axons requires microtubules but not actin filaments
Transport of neurofilaments in growing axons requires microtubules but not actin filaments
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DOI：
10.1002/jnr.20399
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发表时间：
2005-02-15
影响因子：
4.2
通讯作者：
Black, MM
中科院分区：
文献类型：
--
作者：
Francis, F;Roy, S;Black, MM
神经丝（NF）聚合物通过缓慢的轴突运输从细胞体传送到轴突尖端，并且该过程的中断涉及几种神经元病理。这种运动发生在顺行和逆行方向，其特征是神经丝的相对快速但短暂的运动，被长时间的停顿中断。目前的研究结合联合收割机药理学治疗，目标肌动蛋白丝或微管与成像的NF聚合物运输在生活轴突检查依赖这些细胞骨架系统的神经丝运输。用绿色荧光蛋白标记的重NF亚基在培养的交感神经元中表达以可视化NF转运。5 μ M latrunculin处理6小时的轴突肌动蛋白丝的耗竭没有检测到的方向性或运输率的NF的影响，但运动事件的频率从1/3.1分钟的成像时间减少到1/4.9分钟。轴突微管解聚使用5 μ M长春碱3小时或5 μ g/ml诺考达唑4-6小时深刻抑制神经丝运输。在92%的处理过的神经元中，未检测到NF转运。这些观察结果表明，肌动蛋白丝是不需要的神经丝运输，虽然他们可能有微妙的影响神经丝运动。相反，神经纤维的轴突运输需要微管，这表明顺行和逆行的神经纤维运输是由微管马达驱动的。(C)2005 Wiley-Liss，Inc.
Neurofilament (NF) polymers are conveyed from cell body to axon tip by slow axonal transport, and disruption of this process is implicated in several neuronal pathologies. This movement occurs in both anterograde and retrograde directions and is characterized by relatively rapid but brief movements of neurofilaments, interrupted by prolonged pauses. The present studies combine pharmacologic treatments that target actin filaments or microtubules with imaging of NF polymer transport in living axons to examine the dependence of neurofilament transport on these cytoskeletal systems. The heavy NF subunit tagged with green fluorescent protein was expressed in cultured sympathetic neurons to visualize NF transport. Depletion of axonal actin filaments by treatment with 5 muM latrunculin for 6 hr had no detectable effect on directionality or transport rate of NFs, but frequency of movement events was reduced from 1/3.1 min of imaging time to 1/4.9 min. Depolymerization of axonal microtubules using either 5 muM vinblastine for 3 hr or 5 mug/ml nocodazole for 4-6 hr profoundly suppressed neurofilament transport. In 92% of treated neurons, NF transport was undetected. These observations indicate that actin filaments are not required for neurofilament transport, although they may have subtle effects on neurofilament movements. In contrast, axonal transport of NFs requires microtubules, suggesting that anterograde and retrograde NF transport is powered by microtubulebased motors. (C) 2005 Wiley-Liss, Inc.