Genetic modifier screens reveal new components that interact with the Drosophila dystroglycan-dystrophin complex |
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Authors: | Kucherenko Mariya M Pantoja Mario Yatsenko Andriy S Shcherbata Halyna R Fischer Karin A Maksymiv Dariya V Chernyk Yaroslava I Ruohola-Baker Hannele |
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Affiliation: | Department of Biochemistry, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington, United States of America. |
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Abstract: | 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. |
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