Kucherenko Mariya M, Pantoja Mario, Yatsenko Andriy S, Shcherbata Halyna R, Fischer Karin A, Maksymiv Dariya V, Chernyk Yaroslava I, Ruohola-Baker Hannele
Department of Biochemistry, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington, United States of America.
PLoS One. 2008 Jun 11;3(6):e2418. doi: 10.1371/journal.pone.0002418.
The Dystroglycan-Dystrophin (Dg-Dys) complex has a capacity to transmit information from the extracellular matrix to the cytoskeleton inside the cell. It is proposed that this interaction is under tight regulation; however the signaling/regulatory components of Dg-Dys complex remain elusive. Understanding the regulation of the complex is critical since defects in this complex cause muscular dystrophy in humans. To reveal new regulators of the Dg-Dys complex, we used a model organism Drosophila melanogaster and performed genetic interaction screens to identify modifiers of Dg and Dys mutants in Drosophila wing veins. These mutant screens revealed that the Dg-Dys complex interacts with genes involved in muscle function and components of Notch, TGF-beta and EGFR signaling pathways. In addition, components of pathways that are required for cellular and/or axonal migration through cytoskeletal regulation, such as Semaphorin-Plexin, Frazzled-Netrin and Slit-Robo pathways show interactions with Dys and/or Dg. These data suggest that the Dg-Dys complex and the other pathways regulating extracellular information transfer to the cytoskeletal dynamics are more intercalated than previously thought.
肌营养不良蛋白聚糖-抗肌萎缩蛋白（Dg-Dys）复合体具有将细胞外基质中的信息传递至细胞内细胞骨架的能力。有人提出这种相互作用受到严格调控；然而，Dg-Dys复合体的信号/调控成分仍不清楚。了解该复合体的调控至关重要，因为该复合体的缺陷会导致人类肌肉萎缩症。为了揭示Dg-Dys复合体的新调控因子，我们使用了模式生物黑腹果蝇，并进行了遗传相互作用筛选，以鉴定果蝇翅脉中Dg和Dys突变体的修饰因子。这些突变体筛选表明，Dg-Dys复合体与参与肌肉功能的基因以及Notch、TGF-β和EGFR信号通路的成分相互作用。此外，通过细胞骨架调控进行细胞和/或轴突迁移所需的信号通路成分，如信号素-丛蛋白、Frazzled-网蛋白和Slit-Robo信号通路，显示出与Dys和/或Dg相互作用。这些数据表明，Dg-Dys复合体和其他调控细胞外信息向细胞骨架动力学传递的信号通路比之前认为的联系更为紧密。
