A novel Drosophila Girdin-like protein is involved in Akt pathway control of cell size.
A novel Drosophila Girdin-like protein is involved in Akt pathway control of cell size.
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DOI：
10.1016/j.yexcr.2009.06.019
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发表时间：
2009-11
影响因子：
3.7
通讯作者：
Aekkachai Puseenam;Y. Yoshioka;R. Nagai;Reina Hashimoto;Osamu Suyari;M. Itoh;A. Enomoto;Masahide Takahashi;M. Yamaguchi
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文献类型：
--
作者：
Aekkachai Puseenam;Y. Yoshioka;R. Nagai;Reina Hashimoto;Osamu Suyari;M. Itoh;A. Enomoto;Masahide Takahashi;M. Yamaguchi
Akt信号通路是众所周知的调节细胞增殖和生长的通路。Girdin是Akt的一种新底物，在Akt调控下的肌动蛋白细胞骨架的组织和细胞运动中起着至关重要的作用。我们在果蝇中发现了一种新的Girdin样蛋白(DGirdin)，它有两种亚型，dGirdin PA和dGirdin PB。DGirdin在N-末端和螺旋线圈结构域上与人Girdin有很高的同源性，而在C-末端结构域上存在分歧。在体内以dGirdin基因的敲除或过表达为特征的转基因果蝇系的建立中，在翼盘细胞中过表达诱导了异位的细胞凋亡，暗示了其在引导细胞凋亡中的作用。敲除果蝇翅膀成像盘细胞中的dGirdin可导致细胞体积缩小。此外，Akt基因剂量的减半加强了这一点，这表明Akt对dGirdin具有正向调节作用。在翼盘中，dGirdin被击倒的细胞显示肌动蛋白细丝断裂。从这些活体分析中，我们得出结论，在Akt信号通路的控制下，dGirdin是肌动蛋白组织和调节适当细胞大小所必需的。
The Akt signaling pathway is well known to regulate cell proliferation and growth. Girdin, a novel substrate of Akt, plays a crucial role in organization of the actin cytoskeleton and cell motility under the control of Akt. We here identified a novel Girdin-like protein in Drosophila (dGirdin), which has two isoforms, dGirdin PA and dGirdin PB. dGirdin shows high homology with human Girdin in the N-terminal and coiled-coil domains, while diverging at the C-terminal domain. On establishment of transgenic fly lines, featuring knockdown or overexpression of dGirdin in vivo, overexpression in the wing disc cells induced ectopic apoptosis, implying a role in directing apoptosis. Knockdown of dGirdin in the Drosophila wing imaginal disc cells resulted in reduction of cell size. Furthermore, this was enhanced by half reduction of the Akt gene dose, suggesting that Akt positively regulates dGirdin. In the wing disc, cells in which dGirdin was knocked down exhibited disruption of actin filaments. From these in vivo analyses, we conclude that dGirdin is required for actin organization and regulation of appropriate cell size under control of the Akt signaling pathway.