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Signaling through the dystrophin glycoprotein complex affects the stress-dependent transcriptome in Drosophila

Deficiencies in the human dystrophin glycoprotein complex (DGC), which links the extracellular matrix with the intracellular cytoskeleton, cause muscular dystrophies, a group of incurable disorders associated with heterogeneous muscle, brain and eye abnormalities. Stresses such as nutrient deprivati...

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Bibliographic Details
Published in:Disease models & mechanisms 2023-01, Vol.16 (1)
Main Authors: Carney, Travis D, Hebalkar, Rucha Y, Edeleva, Evgeniia, Çiçek, Ibrahim Ömer, Shcherbata, Halyna R
Format: Article
Language:English
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Summary:Deficiencies in the human dystrophin glycoprotein complex (DGC), which links the extracellular matrix with the intracellular cytoskeleton, cause muscular dystrophies, a group of incurable disorders associated with heterogeneous muscle, brain and eye abnormalities. Stresses such as nutrient deprivation and aging cause muscle wasting, which can be exacerbated by reduced levels of the DGC in membranes, the integrity of which is vital for muscle health and function. Moreover, the DGC operates in multiple signaling pathways, demonstrating an important function in gene expression regulation. To advance disease diagnostics and treatment strategies, we strive to understand the genetic pathways that are perturbed by DGC mutations. Here, we utilized a Drosophila model to investigate the transcriptomic changes in mutants of four DGC components under temperature and metabolic stress. We identified DGC-dependent genes, stress-dependent genes and genes dependent on the DGC for a proper stress response, confirming a novel function of the DGC in stress-response signaling. This perspective yields new insights into the etiology of muscular dystrophy symptoms, possible treatment directions and a better understanding of DGC signaling and regulation under normal and stress conditions.
ISSN:1754-8403
1754-8411
DOI:10.1242/dmm.049862