Differentiated neurons retain the capacity to generate axons from dendrites
Differentiated neurons retain the capacity to generate axons from dendrites
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DOI：
10.1016/s0960-9822(00)00807-1
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发表时间：
2000-11-16
期刊：
影响因子：
9.2
通讯作者：
Dotti, CG
中科院分区：
文献类型：
--
作者：
Bradke, F;Dotti, CG
在靠近细胞体处切断形态极化的神经元（第3阶段）的轴突会导致另一个神经突作为轴突生长[1 - 3]。然而，第3阶段的神经元仍然缺乏轴突和树突蛋白的分子分离。在第4阶段（培养4 - 5天），当微管相关蛋白2（MAP - 2）和谷氨酸受体亚基GluR1等蛋白定位于树突并从轴突消失时，轴突和树突区室获得其独特的组成[4,5]。我们研究了在轴突和树突形成其独特的细胞骨架结构并获得其特定的膜成分后，培养的海马神经元是否保留轴突/树突的可塑性。我们发现第4阶段神经元的轴突切断会使一个树突转变为轴突。利用轴突和树突标记物，我们测试了细胞骨架的变化是否会导致类似的转变，并且发现肌动蛋白解聚在未极化的神经元中诱导出多个轴突。此外，从形态和分子上都极化的细胞中去除肌动蛋白丝也会导致从已有的树突生长出多个轴突。这些结果意味着即使在发生分子分离之后，树突仍保留成为轴突的潜力，并且树突的命运取决于肌动蛋白细胞骨架的完整性。
Cutting the axon of a morphologically polarized neuron (stage 3) close to the cell body causes another neurite to grow as an axon [1-3]. Stage 3 neurons still lack molecular segregation of axonal and dendritic proteins, however. Axonal and dendritic compartments acquire their distinct composition at stage 4 (4-5 days in culture), when proteins such as the microtubule-associated protein 2 (MAP-2) and the glutamate receptor subunit GluR1 localize to the dendrites and disappear from the axon [4,5]. We investigated whether cultured hippocampal neurons retained axon/dendrite plasticity after axons and dendrites have created their distinct cytoskeletal architecture and acquired their specific membrane composition. We found that axotomy of stage 4 neurons transformed a dendrite into an axon. Using axonal and dendritic markers, we tested whether cytoskeletal changes could cause similar transformations, and found that actin depolymerization induced multiple axons in unpolarized neurons. Moreover, depletion of actin filaments from both morphologically and molecularly polarized cells also resulted in the growth of multiple axons from pre-existing dendrites. These results imply that dendrites retain the potential to become axons even after molecular segregation has occurred and that the dendritic fate depends on the integrity of the actin cytoskeleton.