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.
Kucherenko
Mariya M
MM
Department of Biochemistry, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington, United States of America.
Pantoja
Mario
M
Yatsenko
Andriy S
AS
Shcherbata
Halyna R
HR
Fischer
Karin A
KA
Maksymiv
Dariya V
DV
Chernyk
Yaroslava I
YI
Ruohola-Baker
Hannele
H
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