del Castillo Urko, Winding Michael, Lu Wen, Gelfand Vladimir I
Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, United States.
Elife. 2015 Dec 28;4:e10140. doi: 10.7554/eLife.10140.
In this study, we investigated how microtubule motors organize microtubules in Drosophila neurons. We showed that, during the initial stages of axon outgrowth, microtubules display mixed polarity and minus-end-out microtubules push the tip of the axon, consistent with kinesin-1 driving outgrowth by sliding antiparallel microtubules. At later stages, the microtubule orientation in the axon switches from mixed to uniform polarity with plus-end-out. Dynein knockdown prevents this rearrangement and results in microtubules of mixed orientation in axons and accumulation of microtubule minus-ends at axon tips. Microtubule reorganization requires recruitment of dynein to the actin cortex, as actin depolymerization phenocopies dynein depletion, and direct recruitment of dynein to the membrane bypasses the actin requirement. Our results show that cortical dynein slides 'minus-end-out' microtubules from the axon, generating uniform microtubule arrays. We speculate that differences in microtubule orientation between axons and dendrites could be dictated by differential activity of cortical dynein.
在本研究中，我们探究了微管马达蛋白如何在果蝇神经元中组织微管。我们发现，在轴突生长的初始阶段，微管呈现混合极性，负端向外的微管推动轴突尖端，这与驱动蛋白-1通过滑动反平行微管来驱动生长相一致。在后期阶段，轴突中的微管方向从混合极性转变为正端向外的均匀极性。动力蛋白敲低会阻止这种重排，并导致轴突中微管方向混合，以及微管负端在轴突尖端积累。微管重组需要动力蛋白被招募到肌动蛋白皮层，因为肌动蛋白解聚模拟了动力蛋白缺失的表型，并且将动力蛋白直接招募到膜上可绕过对肌动蛋白的需求。我们的结果表明，皮层动力蛋白从轴突上滑动“负端向外”的微管，产生均匀的微管阵列。我们推测，轴突和树突之间微管方向的差异可能由皮层动力蛋白的不同活性决定。
