INHIBITION OF NEURITE POLARITY BY TAU ANTISENSE OLIGONUCLEOTIDES IN PRIMARY CEREBELLAR NEURONS
INHIBITION OF NEURITE POLARITY BY TAU ANTISENSE OLIGONUCLEOTIDES IN PRIMARY CEREBELLAR NEURONS
复制标题
DOI：
10.1038/343461a0
复制
发表时间：
1990-02-01
期刊：
影响因子：
64.8
通讯作者：
KOSIK, KS
中科院分区：
文献类型：
--
作者：
CACERES, A;KOSIK, KS
培养中的神经元可以具有基本上不同的形态，这允许它们的细胞学鉴定和将它们的神经突识别为轴突或树突。微管可能具有通过选择性稳定空间上不同的微管子集来确定形态的作用。神经突的可塑性与其组成部分微管的稳定性呈负相关：生长锥中的微管非常动态，并且在初始神经突中有标记亚基的连续掺入1，而在成熟神经突中，微管高度稳定2。微管相关蛋白与微管的结合很可能有助于这种稳定性。分离培养的小脑神经元最初延伸探索性神经突，经过一段相对恒定的时间后，变得极化4。当单个神经突的长度超过其他神经突时，极性变得明显。这些稳定的神经突不再经历初始神经突的收缩和延伸，并呈现出轴突和树突的许多特征。我们现在已经研究了神经元微管相关蛋白tau在轴突极化中的作用，通过向培养基中加入反义寡核苷酸来选择性地抑制tau蛋白的表达。虽然最初的探索性神经突的延伸正常发生，神经突的不对称性被抑制的失败，阐述了轴突。
NEURONS in culture can have fundamentally distinct morphologies which permit their cytological identification and the recognition of their neurites as axons or dendrites. Microtubules may have a role in determining morphology by the selective stabilization of spatially distinct microtubule subsets. The plasticity of a neurite correlates inversely with the stability of its component microtubules: microtubules in growth cones are very dynamic, and in initial neurites there is continuous incorporation of labelled subunits1, whereas in mature neurites, microtubules are highly stabilized2. The binding of microtubule-associated proteins to the microtubules very probably contributes to this stability. Cerebellar neurons in dissociated culture initially extend exploratory neurites and, after a relatively constant interval, become polarized4. Polarity becomes evident when a single neurite exceeds the others in length. These stable neurites cease to undergo the retractions and extensions characteristic of initial neurites and assume many features of axons and dendrites. We have now studied the role of the neuronal microtubule-associate protein tau in neurite polarization by selectively inhibiting tau expression by the addition of antisense oligonucleotides to the culture media. Although the extension of initial exploratory neurites occurred normally, neurite asymmetry was inhibited by the failure to elaborate an axon.