Characterization of the dystrophin‐associated protein complex by mass spectrometry

Abstract

The dystrophin‐associated protein complex (DAPC) is a highly organized multiprotein complex that plays a pivotal role in muscle fiber structure integrity and cell signaling. The complex is composed of three distinct interacting subgroups, intracellular peripheral proteins, transmembrane glycoproteins, and extracellular glycoproteins subcomplexes. Dystrophin protein nucleates the DAPC and is important for connecting the intracellular actin cytoskeletal filaments to the sarcolemma glycoprotein complex that is connected to the extracellular matrix via laminin, thus stabilizing the sarcolemma during muscle fiber contraction and relaxation. Genetic mutations that lead to lack of expression or altered expression of any of the DAPC proteins are associated with different types of muscle diseases. Hence characterization of this complex in healthy and dystrophic muscle might bring insights into its role in muscle pathogenesis. This review highlights the role of mass spectrometry in characterizing the DAPC interactome as well as post‐translational glycan modifications of some of its components such as α‐dystroglycan. Detection and quantification of dystrophin using targeted mass spectrometry are also discussed in the context of healthy versus dystrophic skeletal muscle.

Comprehensive functional characterization of SGCB coding variants predicts pathogenicity in limb-girdle muscular dystrophy type R4/2E

“…Recessive mutations in β-sarcoglycan (SGCB) cause limb-girdle muscular dystrophy type R4/2E (LGMDR4/2E), resulting in muscle wasting, progressive weakness, degeneration of skeletal muscle, and often premature death (1,2). β-Sarcoglycan is a key component of the dystrophin-associated protein complex (3)(4)(5). In muscle cells, the dystrophin-associated protein complex localizes to the membrane and connects the intracellular cytoskeleton to the extracellular matrix, allowing for coordinated force production in muscle.…”