Department of Applied Biology, Insect Biomedical Research Center, Kyoto Institute of Technology, Sakyo-ku, Kyoto 606-8585, Japan.
Front Biosci (Landmark Ed). 2010 Jun 1;15(3):1164-71. doi: 10.2741/3668.
A novel substrate of Akt/PKB designated as Girdin (griders of actin filaments) has been identified in mammals and characterized as an actin-binding protein. A Girdin-like protein has been identified in Drosophila, which has two isoforms, dGirdin PA and dGirdin PB. Knockdown of dGirdin in the Drosophila wing imaginal disc cells resulted in reduction of cell size and this was enhanced by half reduction of the Akt gene dose. Furthermore the dGirdin-knockdown wing disc cells exhibited severe 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. Human Girdin plays important roles in cancer progression and angiogenesis. Therefore Girdin and its interacting proteins could be potential pharmaceutical targets for cancer therapies and tumor angiogenesis. Possible use of the Drosophila Girdin model in understanding the mechanisms of cancer progression and in developing preventive and therapeutic strategies will be discussed.
一种新的 Akt/PKB 底物，即肌动蛋白丝的格栅蛋白（Girdin），已在哺乳动物中被鉴定，并被表征为一种肌动蛋白结合蛋白。果蝇中也鉴定出一种 Girdin 样蛋白，它有两种同工型，dGirdin PA 和 dGirdin PB。在果蝇翅imaginal 盘细胞中敲低 dGirdin 会导致细胞大小减小，而 Akt 基因剂量减半会增强这种减小。此外，dGirdin 敲低的翅盘细胞表现出肌动蛋白丝的严重紊乱。从这些体内分析中，我们得出结论，dGirdin 是肌动蛋白组织所必需的，并且在 Akt 信号通路的控制下调节适当的细胞大小。人 Girdin 在癌症进展和血管生成中发挥重要作用。因此，Girdin 及其相互作用蛋白可能是癌症治疗和肿瘤血管生成的潜在药物靶点。将果蝇 Girdin 模型用于理解癌症进展的机制，并开发预防和治疗策略，将是一个有意义的讨论方向。
