Ahmad F J, Baas P W
Department of Anatomy, University of Wisconsin Medical School, Madison 53706, USA.
J Cell Sci. 1995 Aug;108 ( Pt 8):2761-9. doi: 10.1242/jcs.108.8.2761.
There is controversy concerning the source of new microtubules required for the development of neuronal axons. We have proposed that microtubules are released from the centrosome within the cell body of the neuron and are then translocated into the axon to support its growth. To investigate this possibility, we have developed an experimental regime that permits us to determine the fate of a small population of microtubules nucleated at the neuronal centrosome. Microtubules within cultured sympathetic neurons were depolymerized with the anti-microtubule drug nocodazole, after which the drug was removed. Microtubules rapidly and specifically reassembled from the centrosome within three minutes of nocodazole removal. At this point, low levels of vinblastine, another anti-microtubule drug, were added to the culture to inhibit further microtubule assembly while not substantially depolymerizing the small population of microtubules that had already assembled at the centrosome. Within minutes, released microtubules were apparent in the cytoplasm, and many of these had already translocated to the cell periphery by ten minutes. By one hour, virtually all of the microtubules had been released from the centrosome and were concentrated at the cell periphery. With increasing time, these microtubules appeared within and progressively farther down developing axons. Nonneuronal cells within the culture also reassembled microtubules at the centrosome, but only a small portion of these microtubules were released. These observations indicate that microtubules were released from the neuronal centrosome and transported into growing axons, and that microtubule release and relocation from the centrosome are especially active in neurons compared to nonneuronal cells.
关于神经元轴突发育所需新微管的来源存在争议。我们提出微管从神经元细胞体中的中心体释放出来,然后转移到轴突中以支持其生长。为了研究这种可能性,我们开发了一种实验方法,使我们能够确定在神经元中心体成核的一小部分微管的命运。用抗微管药物诺考达唑使培养的交感神经元内的微管解聚,之后去除该药物。在去除诺考达唑后的三分钟内,微管迅速且特异性地从中心体重组。此时,向培养物中加入低水平的另一种抗微管药物长春花碱,以抑制进一步的微管组装,同时又不会使已经在中心体组装的一小部分微管大量解聚。几分钟内,释放的微管在细胞质中可见,其中许多在十分钟时已转移到细胞周边。到一小时时,几乎所有微管都已从中心体释放并集中在细胞周边。随着时间的增加,这些微管出现在正在发育轴突内并逐渐向更远的地方延伸。培养物中的非神经元细胞也在中心体重组微管,但这些微管中只有一小部分被释放。这些观察结果表明微管从神经元中心体释放并运输到正在生长的轴突中,并且与非神经元细胞相比,微管从中心体的释放和重新定位在神经元中特别活跃。