Fig. 1.

DGC-dependent signaling exerts a defined transcriptional response. (A) Schematic of the DGC and associated proteins. The transmembrane protein Dystroglycan (Dg) is the core component of the complex. Its glycosylated extracellular domain associates with the extracellular matrix, whereas its intracellular portion associates with Dystrophin (Dys) and Syntrophin (Syn), which can act as structural and signaling scaffolds, attaching to the intracellular cytoskeleton as well as to signaling molecules such as nitric oxide synthase (Nos). The nitric oxide (NO) produced by Dys-associated Nos can nitrosylate intracellular proteins such as histone deacetylases (HDACs), affecting the expression of downstream genes. (B) Numbers of genes found to be dysregulated in flies mutant for each of four DGC components: Dg (DgO55/DgO86), Dys [Df(3R)Exel6184], Syn1 [ΔSyn15-2/Df(3L)BSC450C] and Nos [ΔNos¹⁵/Df(2L)BSC230]. The numbers of dysregulated genes ranged from 281 for Syn1 to 513 for Dys. The gray rectangles represent the 46 genes that are dysregulated in all four mutants. (C) Heat map illustrating the 46 genes that are dysregulated in all four mutants assayed. Eleven genes are upregulated and 33 downregulated in all mutants; only two genes, LysX and mtrm, are differentially regulated depending on the genotype. (D) STRING-based clustering of the gene products of the 46 genes that are dysregulated in all four DGC mutants. The clusters are labeled according to the functions and processes in which the genes are involved. Gray lines indicate physical interactions, both putative and experimentally determined; different shades of gray are used for contrast purposes.