Dissecting muscle and neuronal disorders in a Drosophila model of muscular dystrophy.
Perturbation in the Dystroglycan (Dg)-Dystrophin (Dys) complex results in muscular dystrophies and brain abnormalities in human. Here we report that Drosophila is an excellent genetically tractable model to study muscular dystrophies and neuronal abnormalities caused by defects in this complex. Using a fluorescence polarization assay, we show a high conservation in Dg-Dys interaction between human and Drosophila. Genetic and RNAi-induced perturbations of Dg and Dys in Drosophila cause cell polarity and muscular dystrophy phenotypes: decreased mobility, age-dependent muscle degeneration and defective photoreceptor path-finding. Dg and Dys are required in targeting glial cells and neurons for correct neuronal migration. Importantly, we now report that Dg interacts with insulin receptor and Nck/Dock SH2/SH3-adaptor molecule in photoreceptor path-finding. This is the first demonstration of a genetic interaction between Dg and InR.
Shcherbata
Halyna R
HR
Department of Biochemistry, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98195, USA.
Yatsenko
Andriy S
AS
Patterson
Larissa
L
Sood
Vanita D
VD
Nudel
Uri
U
Yaffe
David
D
Baker
David
D
Ruohola-Baker
Hannele
H
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D030801:Animals, Genetically Modified; D002465:Cell Movement / Q000235:genetics; D016764:Cell Polarity; D004195:Disease Models, Animal; D004330:Drosophila; D049030:Dystroglycans / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D016189:Dystrophin / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D009137:Muscular Dystrophy, Animal / Q000209:etiology / Q000235:genetics*; D009154:Mutation; D009421:Nervous System Malformations / Q000235:genetics*; D015513:Oncogene Proteins / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D016189:Dystrophin; C078332:Nck protein; D015513:Oncogene Proteins; D049030:Dystroglycans