ASSEMBLY OF MICROTUBULES AT THE TIP OF GROWING AXONS

ASSEMBLY OF MICROTUBULES AT THE TIP OF GROWING AXONS
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DOI:
10.1038/321788a0
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发表时间:
1986-06-19
期刊:
影响因子:
64.8
通讯作者:
CHAPMAN, K
CHAPMAN, K
中科院分区:
综合性期刊1区
文献类型:
--
作者:
BAMBURG, JR;BRAY, D;CHAPMAN, K

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在发育中的神经系统中,轴突的生长取决于微管的伸长,而微管是轴突的主要纵向结构元素1,2。目前尚不清楚轴突中的单个微管是否在其近端伸长,靠近细胞体,然后向前移动到延长的轴突中,或者微管亚基是否被运输到轴突的尖端并在那里组装到微管的自由端。前一种可能性得到了成熟神经缓慢轴突运输研究的支持,该研究推断微管组装主要发生在神经元细胞体3,4。相比之下,轴突中微管的极性(其“正”端或“快速”端位于细胞体的远端)表明,组装发生在轴突的生长尖端或生长锥。我们通过局部应用秋水仙碱(n -去乙酰- n -甲基秋水仙碱)和其他改变微管稳定性的药物来解决这个问题,这些药物用于组织培养中生长的分离神经细胞的不同区域。我们发现,对这些药物的敏感性在生长锥处最高,至少有两个数量级,这表明这是轴突生长过程中微管组装的主要部位。
The growth of axons in the developing nervous system depends on the elongation of the microtubules that form their principal longitudinal structural element1,2. It is not known whether individual microtubules in the axon elongate at their proximal ends, close to the cell body, and then move forward into the lengthening axon, or whether tubulin subunits are transported to the tip of the axon and assembled there onto the free ends of microtubules. The former possibility is supported by studies of slow axonal transport in mature nerves from which it has been deduced that microtubule assembly occurs principally at the neuronal cell body3,4. By contrast, the polarity of microtubules in axons, which have their ‘plus’ or ‘fast-growing’ ends distal to the cell body5, suggests that assembly occurs at the growing tip, or growth cone, of the axon. We have addressed this question by topically applying Colcemid (N-desacetyl-N-methylcolchicine), and other drugs which alter microtubule stability, to different regions of isolated nerve cells growing in tissue culture. We find that the sensitivity to these drugs is greatest at the growth cone by at least two orders of magnitude, suggesting that this is a major site of microtubule assembly during axonal growth.