Temasek Life Sciences Laboratory, National University of Singapore, Singapore, Singapore.
Department of Biological Sciences, National University of Singapore, Singapore, Singapore.
EMBO Rep. 2021 Oct 5;22(10):e52679. doi: 10.15252/embr.202152679. Epub 2021 Aug 2.
It has long been thought that microtubule disassembly, one of the earliest cellular events, contributes to neuronal pruning and neurodegeneration in development and disease. However, how microtubule disassembly drives neuronal pruning remains poorly understood. Here, we conduct a systematic investigation of various microtubule-destabilizing factors and identify exchange factor for Arf6 (Efa6) and Stathmin (Stai) as new regulators of dendrite pruning in ddaC sensory neurons during Drosophila metamorphosis. We show that Efa6 is both necessary and sufficient to regulate dendrite pruning. Interestingly, Efa6 and Stai facilitate microtubule turnover and disassembly prior to dendrite pruning without compromising the minus-end-out microtubule orientation in dendrites. Moreover, our pharmacological and genetic manipulations strongly support a key role of microtubule disassembly in promoting dendrite pruning. Thus, this systematic study highlights the importance of two selective microtubule destabilizers in dendrite pruning and substantiates a causal link between microtubule disassembly and neuronal pruning.
长期以来，人们一直认为微管解聚是最早的细胞事件之一，有助于发育和疾病过程中的神经元修剪和神经退行性变。然而，微管解聚如何驱动神经元修剪仍然知之甚少。在这里，我们对各种微管解聚因子进行了系统研究，并确定了 Arf6 的交换因子（Efa6）和 Stathmin（Stai）是果蝇变态过程中ddaC 感觉神经元中树突修剪的新调节因子。我们表明，Efa6 既是必需的也是充分的，以调节树突修剪。有趣的是，Efa6 和 Stai 在树突修剪之前促进微管周转和解聚，而不会损害树突中负端向外的微管取向。此外，我们的药理学和遗传学操作强烈支持微管解聚在促进树突修剪中的关键作用。因此，这项系统研究强调了两种选择性微管解聚剂在树突修剪中的重要性，并证实了微管解聚与神经元修剪之间的因果关系。
