Genetic modifier screens reveal new components that interact with the Drosophila dystroglycan-dystrophin complex

• Published in: PloS one 2008-06, Vol.3 (6), p.e2418-e2418
• Main Authors: Kucherenko, Mariya M, Pantoja, Mario, Yatsenko, Andriy S, Shcherbata, Halyna R, Fischer, Karin A, Maksymiv, Dariya V, Chernyk, Yaroslava I, Ruohola-Baker, Hannele
• Format: Article
• Language: English
• Subjects: Age; Animals; Biochemistry; Biotechnology; Bone morphogenetic proteins; Cell adhesion & migration; Cytoskeleton; Defects; Drosophila; Drosophila melanogaster; Drosophila melanogaster - genetics; Drosophila melanogaster - metabolism; Drosophila Proteins - metabolism; Dystroglycan; Dystroglycans - metabolism; Dystrophin; Dystrophin - metabolism; Dystrophy; Epidermal growth factor receptors; ErbB Receptors - metabolism; Extracellular matrix; Genetic aspects; Genetic screening; Genetics; Genetics and Genomics/Genetics of Disease; Information transfer; Insects; Medicine; Muscular dystrophy; Mutants; Mutation; Phosphatase; Photoreceptors; Proteins; Receptors, Notch - metabolism; Regulators; Robo protein; Rodents; Screens; Signal Transduction; Slit protein; Stem cells; Transforming Growth Factor beta - metabolism; Transforming growth factors
• ISSN: 1932-6203; 1932-6203
• 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.