The role of the dystrophin glycoprotein complex in muscle cell mechanotransduction

A review of the function of the Dystrophic Glycoprotein Complex (DGC) in mechanosignaling provides an overview of the various components of DGC and potential mechanopathogenic mechanisms, particularly as they relate to muscular dystrophy. Dystrophin is the central protein of the dystrophin-glycoprotein complex (DGC) in skeletal and heart muscle cells. Dystrophin connects the actin cytoskeleton to the extracellular matrix (ECM). Severing the link between the ECM and the intracellular cytoskeleton has a devastating impact on the homeostasis of skeletal muscle cells, leading to a range of muscular dystrophies. In addition, the loss of a functional DGC leads to progressive dilated cardiomyopathy and premature death. Dystrophin functions as a molecular spring and the DGC plays a critical role in maintaining the integrity of the sarcolemma. Additionally, evidence is accumulating, linking the DGC to mechanosignalling, albeit this role is still less understood. This review article aims at providing an up-to-date perspective on the DGC and its role in mechanotransduction. We first discuss the intricate relationship between muscle cell mechanics and function, before examining the recent research for a role of the dystrophin glycoprotein complex in mechanotransduction and maintaining the biomechanical integrity of muscle cells. Finally, we review the current literature to map out how DGC signalling intersects with mechanical signalling pathways to highlight potential future points of intervention, especially with a focus on cardiomyopathies.

Automated summary

This review summarizes the function and mechanisms of the Dystrophic Glycoprotein Complex (DGC) in mechanosignaling, with a particular focus on its role in muscular dystrophy. Dystrophin plays a crucial role in connecting the actin cytoskeleton to the extracellular matrix, and loss of a functional DGC leads to various muscular dystrophies and dilated cardiomyopathy. Evidence suggests that the DGC is involved in mechanosignaling, although this role is not fully understood. This review aims to provide an up-to-date perspective on the DGC's role in mechanotransduction and potential future interventions.