SRPS associated protein WDR60 regulates the multipolar-to-bipolar transition of migrating neurons during cortical development.
SRPS associated protein WDR60 regulates the multipolar-to-bipolar transition of migrating neurons during cortical development.
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SRPS 相关蛋白 WDR60 调节皮质发育过程中迁移神经元的多极到双极转变。
DOI：
10.1038/s41419-020-03363-3
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发表时间：
2021-01-12
影响因子：
9
通讯作者：
Xu Z
中科院分区：
文献类型：
--
作者：
Li C;Zheng Y;Zheng Y;Xu Z
在短肋多指综合征（SRPS I-V）中发现了WD40重复结构域60 （WDR60）突变，短肋多指综合征是一组以短肋、多指和一系列骨骼外表型为特征的致命先天性疾病。然而，其潜在机制尚不清楚。在这里，我们报道WDR60对胚胎发育至关重要，并在大脑发育过程中新生儿神经元的多极-双极转换和迁移中发挥关键作用。从机械上，我们发现WDR60位于微管组织中心，控制微管组织，并可能控制细胞成分的运输。重要的是，Wdr60敲低引起的迁移缺陷可以通过α-Tubulin α-TubulinK40Q（一种乙酰化模拟突变体）的稳定形式来修复。这些发现确定了WDR60的非纤毛功能，并为其生物学功能以及与SRPS相关的WDR60缺乏症的发病机制提供了见解。
Mutations of WD40 repeat domain 60 (WDR60) have been identified in short-rib polydactyly syndromes (SRPS I–V), a group of lethal congenital disorders characterized by short ribs, polydactyly, and a range of extraskeletal phenotypes. However, the underlying mechanism is still unclear. Here, we report that WDR60 is essential for embryonic development and plays a critical role in the multipolar-bipolar transition and migration of newborn neurons during brain development. Mechanically, we found that WDR60 was located at the microtubule-organizing center to control microtubule organization and possibly, the trafficking of cellular components. Importantly, the migration defect caused by Wdr60 knockdown could be rescued by the stable form of α-Tubulin, α-TubulinK40Q (an acetylation-mimicking mutant). These findings identified a non-cilia function of WDR60 and provided insight into its biological function, as well as the pathogenesis of WDR60 deficiency associated with SRPS.
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影响因子：
4
作者：
Asante D;Stevenson NL;Stephens DJ
通讯作者：
Stephens DJ
影响因子：
16.2
作者：
Geschwind DH;Rakic P
通讯作者：
Rakic P
纤毛：细胞天线和中央加工单元。
影响因子：
19
作者：
Malicki JJ;Johnson CA
通讯作者：
Johnson CA
影响因子：
11.4
作者：
Xu, ZH;Kukekov, NV;Greene, LA
通讯作者：
Greene, LA
影响因子：
64.5
作者：
Ding, S;Wu, XH;Xu, T
通讯作者：
Xu, T