Patronin governs minus-end-out orientation of dendritic microtubules to promote dendrite pruning in Drosophila
Patronin governs minus-end-out orientation of dendritic microtubules to promote dendrite pruning in Drosophila
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DOI：
10.7554/elife.39964
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发表时间：
2019-03
期刊：
影响因子：
7.7
通讯作者：
Yan Wang;Menglong Rui;Quan Tang;Shufeng Bu;F. Yu
中科院分区：
文献类型：
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作者：
Yan Wang;Menglong Rui;Quan Tang;Shufeng Bu;F. Yu
在果蝇蜕变过程中，IV类ddaC神经元特异性地修剪幼虫的树突，而不影响轴突。ddac将微管的负端分布到树突上，而正端分布到轴突上。然而，MT -末端结合蛋白在树突特异性剪枝中的需求仍然是完全未知的。在这里，我们发现了一种负端结合蛋白Patronin，它在ddaC树突修剪中起着至关重要的剂量敏感作用。CKK结构域对Patronin在树突修剪中的功能起重要作用。此外，我们发现，光顾蛋白敲除和过表达都导致ddaC树突中MT -end-out的急剧减少和伴随的MT -end-out的增加，这表明光顾蛋白稳定了树突中-end-out的MT。同样，光顾蛋白突变神经元中Klp10A MT解聚合酶的衰减显著恢复了树突中-end-out的MT，从而挽救了树突修剪缺陷。因此，我们的研究表明，光顾蛋白在树突中定向负端外MT阵列，主要通过拮抗Klp10A活性来促进树突特异性修剪。编辑说明：本文经过编辑过程，作者决定如何回应同行评议中提出的问题。评审编辑的评估是小问题仍未解决（见决定函）。
Class IV ddaC neurons specifically prune larval dendrites without affecting axons during Drosophila metamorphosis. ddaCs distribute the minus ends of microtubules (MTs) to dendrites but the plus ends to axons. However, a requirement of MT minus-end-binding proteins in dendrite-specific pruning remains completely unknown. Here, we identified Patronin, a minus-end-binding protein, for its crucial and dose-sensitive role in ddaC dendrite pruning. The CKK domain is important for Patronin’s function in dendrite pruning. Moreover, we show that both patronin knockdown and overexpression resulted in a drastic decrease of MT minus ends and a concomitant increase of plus-end-out MTs in ddaC dendrites, suggesting that Patronin stabilizes dendritic minus-end-out MTs. Consistently, attenuation of Klp10A MT depolymerase in patronin mutant neurons significantly restored minus-end-out MTs in dendrites and thereby rescued dendrite-pruning defects. Thus, our study demonstrates that Patronin orients minus-end-out MT arrays in dendrites to promote dendrite-specific pruning mainly through antagonizing Klp10A activity. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that minor issues remain unresolved (see decision letter).