Genetic modifier screens reveal new components that interact with the Drosophila dystroglycan-dystrophin complex.
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.
Department of Biochemistry, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington, United States of America.
Mariya M
MM
Kucherenko
Mario
M
Pantoja
Andriy S
AS
Yatsenko
Halyna R
HR
Shcherbata
Karin A
KA
Fischer
Dariya V
DV
Maksymiv
Yaroslava I
YI
Chernyk
Hannele
H
Ruohola-Baker
D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D049030:Dystroglycans / Q000378:metabolism*; D016189:Dystrophin / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D009154:Mutation; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism
D029721:Drosophila Proteins; D016189:Dystrophin; C497759:N protein, Drosophila; D051880:Receptors, Notch; D016212:Transforming Growth Factor beta; D049030:Dystroglycans; D066246:ErbB Receptors