F-actin rearrangement is regulated by mTORC2/Akt/Girdin in mouse fertilized eggs.
F-actin rearrangement is regulated by mTORC2/Akt/Girdin in mouse fertilized eggs.
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小鼠受精卵中 F-肌动蛋白重排受 mTORC2/Akt/Girdin 调节
DOI：
10.1111/cpr.12285
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发表时间：
2016-12
影响因子：
8.5
通讯作者：
Yu B
中科院分区：
文献类型：
--
作者：
Wu D;Yu D;Wang X;Yu B
在小鼠受精卵中，肌动蛋白细胞骨架的正确组装和分布与早期胚胎的卵裂密切相关。然而，在小鼠受精卵中，负责调节肌动蛋白细胞骨架的机制和相关因素尚不清楚。在本研究中，mTORC2、PKB/Akt和Girdin通过调节肌动蛋白细胞骨架的分布来调节小鼠受精卵的分裂。RNA干扰(RNAi)介导的mTORC2、Akt1或Girdin的缺失扰乱了F-肌动蛋白重排，并强烈抑制了卵子的发育。PKB/Akt已被证明是mTORC2信号通路的下游靶点。Girdin是一种新发现的肌动蛋白交联剂，已被证明是Akt信号通路的下游靶标。此外，Akt1和Gridin的磷酸化都受到mTORC2基因敲除的影响。AKT1通过GRADIN介导的F-肌动蛋白重排正向调控小鼠受精卵的发育。因此，Glydin似乎可能是Akt1介导的信号通路的下游靶点。综上所述，本研究旨在证明mTORC2/Akt参与F-肌动蛋白组装在小鼠受精卵早期卵裂中的作用。在小鼠受精卵中，肌动蛋白细胞骨架的正确组装和分布与早期胚胎的卵裂密切相关。然而，在哺乳动物中，特别是在小鼠受精卵中，负责调节肌动蛋白细胞骨架的机制和涉及的因素尚不清楚。本研究的目的是通过调节肌动蛋白细胞骨架的分布，确定mTORC2、PKB/Akt和Girdin在小鼠受精卵早期发育中的作用。免疫荧光染色和激光扫描共聚焦显微镜观察mTORC2 shRNA、Akt siRNA和Girdin siRNA处理后F-肌动蛋白的变化。Western免疫印迹法检测Se1417处磷酸化Girdin的表达水平。用解剖显微镜计数细胞分裂百分率。RNA干扰(RNAi)介导的mTORC2、Akt1或Girdin的缺失扰乱了F-肌动蛋白重排，并显著抑制了小鼠受精卵的发育。PKB/Akt已被证明是mTORC2信号通路的下游靶点。新发现的肌动蛋白交联物Girdin已被证明是Akt信号通路的下游靶点。此外，Akt1和Girdin的磷酸化都受到mTORC2基因敲除的影响。AKT1通过Girdin介导的F-肌动蛋白重排正向调节小鼠受精卵的发育。Girdin可能是Akt1介导的信号通路的下游靶点。综上所述，本研究旨在证明mTORC2/Akt通过Girdin的功能参与小鼠受精卵早期卵裂过程中F-肌动蛋白的组装。
In mouse fertilized eggs, correct assembly and distribution of the actin cytoskeleton are intimately related to cleavage in early‐stage embryos. However, in mouse fertilized eggs, mechanisms and involved factors responsible for regulating the actin cytoskeleton are poorly defined. In this study, mTORC2, PKB/Akt and Girdin were found to modulate division of mouse fertilized eggs by regulating distribution of the actin cytoskeleton. RNA interference (RNAi)‐mediated depletion of mTORC2, Akt1 or Girdin disrupted F‐actin rearrangement and strongly inhibited egg development. PKB/Akt has been proven to be a downstream target of the mTORC2 signalling pathway. Girdin, a newly found actin cross‐linker, has been proven to be a downstream target of the Akt signalling pathway. Furthermore, phosphorylation of both Akt1 and girdin was affected by knockdown of mTORC2. Akt1 positively regulated development of the mouse fertilized eggs by girdin‐mediated F‐actin rearrangement. Thus it seems that girdin could be a downstream target of the Akt1‐mediated signalling pathway. Collectively, this study aimed to prove participation of mTORC2/Akt in F‐actin assembly in early‐stage cleavage of mouse fertilized eggs via the function of girdin. In mouse fertilized eggs, the proper assembly and distribution of actin cytoskeleton is intimately related with the cleavage of early‐stage embryo. However, in mammals, especially in mouse fertilized eggs, the mechanisms and involved factors responsible for regulating the actin cytoskeleton are poorly defined. The aim of this study was to determine the role of mTORC2,PKB/Akt and Girdin in early development of fertilized mouse eggs, via regulating the distribution of actin cytoskeleton. Changes of F‐actin after treatting with mTORC2 shRNA, Akt siRNA or Girdin siRNA were observed by Immunofluorescence staining and laser‐scanning confocal microscopy. Levels of phosphorylated Girdin at Se1417 were detected by Western immunoblotting. Percentages of cells undergoing division were determined by counting, using a dissecting microscope. RNA interference (RNAi)‐mediated depletion of mTORC2, Akt1 or Girdin disrupts F‐actin rearrangement, and remarkably inhibited the development of mouse‐fertilized eggs. PKB/Akt has been proved to be a downstream target of the mTORC2 signaling pathway. Girdin, the newly found actin‐cross linker, has been proved to be a downstream target of the Akt signaling pathway. Furthermore phosphorylation of both Akt1 and Girdin were affected by knockdown of mTORC2. Akt1 positively regulates the development of mouse‐fertilized eggs by Girdin mediated F‐actin rearrangement. Girdin could be a downstream target of the Akt1‐mediated signaling pathway. Collectively, this study aimed to prove the participation of mTORC2/Akt in F‐actin assembling in early‐stage cleavage of mouse fertilized eggs via the function of Girdin.
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