Biochemistry and Molecular Biology and the Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
Biochemistry and Molecular Biology and the Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
Dev Biol. 2022 Jun;486:56-70. doi: 10.1016/j.ydbio.2022.03.009. Epub 2022 Mar 25.
Many neurons in bilaterian animals are polarized with functionally distinct axons and dendrites. Microtubule polarity, microtubule stability, and the axon initial segment (AIS) have all been shown to influence polarized transport in neurons. Each of these cytoskeletal cues could act independently to control axon and dendrite identity, or there could be a hierarchy in which one acts upstream of the others. Here we test the hypothesis that microtubule polarity acts as a master regulator of neuronal polarity by using a Drosophila genetic background in which some dendrites have normal minus-end-out microtubule polarity and others have the axonal plus-end-out polarity. In these mosaic dendrite arbors, we found that ribosomes, which are more abundant in dendrites than axons, were reduced in plus-end-out dendrites, while an axonal cargo was increased. In addition, we determined that microtubule stability was different in plus-end-out and minus-end-out dendrites, with plus-end-out ones having more stable microtubules like axons. Similarly, we found that ectopic diffusion barriers, like those at the AIS, formed at the base of dendrites with plus-end-out regions. Thus, changes in microtubule polarity were sufficient to rearrange other cytoskeletal features associated with neuronal polarization. However, overall neuron shape was maintained with only subtle changes in branching in mosaic arbors. We conclude that microtubule polarity can act upstream of many aspects of intracellular neuronal polarization, but shape is relatively resilient to changes in microtubule polarity in vivo.
许多两侧对称动物的神经元具有功能上不同的轴突和树突,呈现极化状态。微管极性、微管稳定性和轴突起始段(AIS)都已被证明会影响神经元中的极化运输。这些细胞骨架线索中的每一个都可以独立地控制轴突和树突的身份,或者可能存在一个层次结构,其中一个线索在其他线索之前起作用。在这里,我们通过使用果蝇遗传背景来测试微管极性作为神经元极性主调控因子的假设,在该背景中,一些树突具有正常的负端向外微管极性,而另一些树突具有轴突的正端向外极性。在这些镶嵌的树突树中,我们发现核糖体在树突中比在轴突中更丰富,在正端向外的树突中减少,而轴突货物增加。此外,我们确定正端向外和负端向外的树突中的微管稳定性不同,正端向外的树突具有与轴突相似的更稳定的微管。同样,我们发现像 AIS 一样的异位扩散障碍形成在具有正端向外区域的树突底部。因此,微管极性的变化足以重新排列与神经元极化相关的其他细胞骨架特征。然而,在镶嵌的树突中,只有分支的细微变化,神经元的整体形状得以保持。我们得出结论,微管极性可以作为细胞内神经元极化许多方面的上游因素,但在体内,形状对微管极性的变化相对具有弹性。