Transport of dendritic microtubules establishes their nonuniform polarity orientation.

Transport of dendritic microtubules establishes their nonuniform polarity orientation.
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DOI:
10.1083/jcb.130.1.93
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发表时间:
1995-07
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Baas PW
Baas PW
中科院分区:
其他
文献类型:
--
作者:
Sharp DJ;Yu W;Baas PW

文献摘要

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产生轴突和树突的未成熟过程中含有微管(MTs),它们的正端均匀地朝向细胞体的远端,这种模式在发育中的轴突中保留下来。相反,发育中的树突逐渐获得不均匀的MT极性取向,这是由于增加了一个相反取向的MT亚群(Baas, P. W., M. M. Black,和G. a . Banker. 1989)。[j] .中国生物医学工程学报,2009(9):391 - 391。理论上,这些负端远端MTs可以局部成核并在树突内组装,也可以在细胞体内成核后转运到树突中。为了区分这些可能性,我们将培养的海马神经元暴露在纳摩尔水平的长春碱中,在其中一个未成熟突起发育成轴突之后,而在其他突起发育成树突之前。在这些水平下,长春花碱作为MTs的动力学稳定剂,抑制进一步的组装,同时不会使现有的MTs实质上解聚。这种处理并没有消除树突分化,树突分化在接下来的两到三天内及时发生。得到的树突比对照组更平坦、更短,但可以通过其超微结构、化学成分和增厚的锥形形态来识别。这些树突的生长伴随着细胞体中mt的减少,表明mt从一个室转移到另一个室。在此期间,实验树突中出现了负端远端微管,这表明树突中不需要新的MT组装来获得不均匀的MT极性取向。负端远端微管在实验树突的更近端区域占主导地位,这表明在这个发育阶段,大多数mt以负端为先导被运输到树突中。这些观察结果表明,从细胞体运输mt是树突发育的一个基本特征,这种运输建立了树突中mt的不均匀极性取向。
The immature processes that give rise to both axons and dendrites contain microtubules (MTs) that are uniformly oriented with their plus- ends distal to the cell body, and this pattern is preserved in the developing axon. In contrast, developing dendrites gradually acquire nonuniform MT polarity orientation due to the addition of a subpopulation of oppositely oriented MTs (Baas, P. W., M. M. Black, and G. A. Banker. 1989. J. Cell Biol. 109:3085-3094). In theory, these minus-end-distal MTs could be locally nucleated and assembled within the dendrite itself, or could be transported into the dendrite after their nucleation within the cell body. To distinguish between these possibilities, we exposed cultured hippocampal neurons to nanomolar levels of vinblastine after one of the immature processes had developed into the axon but before the others had become dendrites. At these levels, vinblastine acts as a kinetic stabilizer of MTs, inhibiting further assembly while not substantially depolymerizing existing MTs. This treatment did not abolish dendritic differentiation, which occurred in timely fashion over the next two to three days. The resulting dendrites were flatter and shorter than controls, but were identifiable by their ultrastructure, chemical composition, and thickened tapering morphology. The growth of these dendrites was accompanied by a diminution of MTs from the cell body, indicating a net transfer of MTs from one compartment into the other. During this time, minus-end-distal microtubules arose in the experimental dendrites, indicating that new MT assembly is not required for the acquisition of nonuniform MT polarity orientation in the dendrite. Minus-end-distal microtubules predominated in the more proximal region of experimental dendrites, indicating that most of the MTs at this stage of development are transported into the dendrite with their minus-ends leading. These observations indicate that transport of MTs from the cell body is an essential feature of dendritic development, and that this transport establishes the nonuniform polarity orientation of MTs in the dendrite.