Bamburg J R, Bray D, Chapman K
Nature. 1986;321(6072):788-90. doi: 10.1038/321788a0.
The growth of axons in the developing nervous system depends on the elongation of the microtubules that form their principal longitudinal structural element. 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 body. By contrast, the polarity of microtubules in axons, which have their 'plus' or 'fast-growing' ends distal to the cell body, 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.
发育中的神经系统中轴突的生长取决于构成其主要纵向结构元件的微管的伸长。目前尚不清楚轴突中的单个微管是否在靠近细胞体的近端伸长,然后向前移动到延长的轴突中,或者微管蛋白亚基是否被运输到轴突的末端并在那里组装到微管的自由端上。成熟神经中慢轴突运输的研究支持了前一种可能性,由此推断微管组装主要发生在神经元细胞体。相比之下,轴突中微管的极性,其“正”端或“快速生长”端位于细胞体的远端,这表明组装发生在轴突的生长末端或生长锥。我们通过在组织培养中生长的分离神经细胞的不同区域局部应用秋水仙酰胺(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。我们发现,生长锥对这些药物的敏感性至少高两个数量级,这表明生长锥是轴突生长过程中微管组装的主要部位。