Genetic link between β-sarcoglycan and the Egfr signaling pathway

Sarcoglycans are a multimeric, integral membrane protein complex that is part of the dystrophin glycoprotein complex. Previous findings suggest that the dystrophin glycoprotein complex plays roles not only in maintaining the mechanical structure of the cell membrane but also in signal transduction. To evaluate the functions of sarcoglycans, we here took advantage of Drosophila, which is useful for screening genetic interactions. Morphological aberrancy was observed in the adult compound eyes of Drosophila β-sarcolgycan (dscgβ) knockdown flies. We also detected genetic interactions between dscgβ and Egfr related genes, such as rhomboid-1, rhomboid-3, and mirror. Furthermore two extra cell types with strong expression of Rhomboid were found in the ommatidia of dscgβ knockdown pupal retina. These cells exhibited phosphorylation of ERKA, suggesting that Egfr signaling is activated via Rhomboid. Through these in vivo analyses, we conclude that dscgβ negatively regulates the Egfr signaling pathway.