Temasek Life Sciences Laboratory, Singapore City, Singapore.
Department of Biological Sciences, National University of Singapore, Singapore City, Singapore.
EMBO J. 2020 May 18;39(10):e103549. doi: 10.15252/embj.2019103549. Epub 2020 Apr 8.
Drosophila class IV ddaC neurons selectively prune all larval dendrites to refine the nervous system during metamorphosis. During dendrite pruning, severing of proximal dendrites is preceded by local microtubule (MT) disassembly. Here, we identify an unexpected role of Mini spindles (Msps), a conserved MT polymerase, in governing dendrite pruning. Msps associates with another MT-associated protein TACC, and both stabilize each other in ddaC neurons. Moreover, Msps and TACC are required to orient minus-end-out MTs in dendrites. We further show that the functions of msps in dendritic MT orientation and dendrite pruning are antagonized by the kinesin-13 MT depolymerase Klp10A. Excessive MT depolymerization, which is induced by pharmacological treatment and katanin overexpression, also perturbs dendritic MT orientation and dendrite pruning, phenocopying msps mutants. Thus, we demonstrate that the MT polymerase Msps is required to form dendritic minus-end-out MTs and thereby promotes dendrite pruning in Drosophila sensory neurons.
果蝇 IV 类 ddaC 神经元在变态期间选择性地修剪所有幼虫树突，以精炼神经系统。在树突修剪过程中，近端树突的切断先于局部微管 (MT) 解体。在这里，我们发现一个意想不到的角色，即 Mini spindles (Msps)，一种保守的 MT 聚合酶，在调控树突修剪中。Msps 与另一种与 MT 相关的蛋白 TACC 结合，并且在 ddaC 神经元中相互稳定。此外，Msps 和 TACC 都需要在树突中定向排列负端向外的 MT。我们进一步表明，msps 在树突 MT 取向和树突修剪中的功能被动力蛋白-13 MT 解聚酶 Klp10A 拮抗。药物处理和katanin 过表达诱导的过度 MT 解聚也会扰乱树突 MT 取向和树突修剪，表现出 msps 突变体的表型。因此，我们证明 MT 聚合酶 Msps 是形成树突负端向外 MT 所必需的，从而促进果蝇感觉神经元的树突修剪。
