Genetic Modifier Screens Reveal New Components that Interact with the Drosophila Dystroglycan-Dystrophin Complex

University of Arkansas, United States of America
PLoS ONE (Impact Factor: 3.23). 02/2008; 3(6):e2418. DOI: 10.1371/journal.pone.0002418
Source: PubMed


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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Available from: Halyna R Shcherbata, Dec 19, 2014
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    • "Gieseler et al. 2000; Mariol & Ségalat 2001), flies (e.g. Kucherenko et al. 2008), and mice (Deconinck et al. 1997) have thus turned to study sensitized strains in an attempt to recapitulate the human phenotype. However, genetic sensitization may limit the applicability of results to MD that occurs in humans with mutations only in dystrophin (Monaco et al. 1986). "
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