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Protein phosphatase PP2A regulates microtubule orientation and dendrite pruning in Drosophila.
EMBO Reports ( IF 6.5 ) Pub Date : 2020-03-18 , DOI: 10.15252/embr.201948843
Menglong Rui 1 , Kay Siong Ng 1 , Quan Tang 1, 2 , Shufeng Bu 1, 2 , Fengwei Yu 1, 2, 3, 4
Affiliation  

Pruning that selectively eliminates inappropriate projections is crucial for sculpting neural circuits during development. During Drosophila metamorphosis, ddaC sensory neurons undergo dendrite-specific pruning in response to the steroid hormone ecdysone. However, the understanding of the molecular mechanisms underlying dendrite pruning remains incomplete. Here, we show that protein phosphatase 2A (PP2A) is required for dendrite pruning. The catalytic (Microtubule star/Mts), scaffolding (PP2A-29B), and two regulatory subunits (Widerborst/Wdb and Twins/Tws) play important roles in dendrite pruning. Functional analyses indicate that PP2A, via Wdb, facilitates the expression of Sox14 and Mical prior to dendrite pruning. Furthermore, PP2A, via Tws, governs the minus-end-out orientation of microtubules (MTs) in the dendrites. Moreover, the levels of Klp10A, a MT depolymerase, increase when PP2A is compromised. Attenuation of Klp10A fully rescues the MT orientation defects in mts or pp2a-29b RNAi ddaC neurons, suggesting that PP2A governs dendritic MT orientation by suppressing Klp10A levels and/or function. Taken together, this study sheds light on a novel function of PP2A in regulating dendrite pruning and dendritic MT polarity in sensory neurons.

中文翻译:

蛋白磷酸酶 PP2A 调节果蝇中的微管方向和树突修剪。

选择性地消除不适当的投影的修剪对于在发育过程中塑造神经回路至关重要。在果蝇变态过程中,ddaC 感觉神经元响应类固醇激素蜕皮激素进行树突特异性修剪。然而,对树突修剪的分子机制的理解仍然不完整。在这里,我们表明蛋白磷酸酶 2A (PP2A) 是树突修剪所必需的。催化(微管星/Mts)、支架(PP2A-29B)和两个调节亚基(Widerborst/Wdb 和 Twins/Tws)在枝晶修剪中起重要作用。功能分析表明,PP2A 通过 Wdb 促进了 Sox14 和 Mical 在树突修剪之前的表达。此外,PP2A 通过 Tws 控制树突中微管 (MTs) 的负端方向。而且,当 PP2A 受损时,MT 解聚酶 Klp10A 的水平会增加。Klp10A 的衰减完全挽救了 mts 或 pp2a-29b RNAi ddaC 神经元中的 MT 方向缺陷,表明 PP2A 通过抑制 Klp10A 水平和/或功能来控制树突 MT 方向。总之,这项研究揭示了 PP2A 在调节感觉神经元中树突修剪和树突 MT 极性方面的新功能。
更新日期:2020-03-18
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