Dystrophin-associated protein complex (DAPC) (DAPC)

The Dystrophin-associated protein complex (DAPC) is a large, multi-component assembly that spans the sarcolemma of skeletal and cardiac muscle fibers, serving as a vital mechanical link between the intracellular F-actin cytoskeleton and the extracellular matrix (laminin) (UniProt P11532). The core of the complex consists of dystrophin, the dystroglycan complex (alpha and beta subunits), sarcoglycans, and dystrobrevins, while also serving as a scaffold for signaling molecules such as neuronal nitric oxide synthase (nNOS) and Par1b (MARK2) (PubMed: 21135508, 20154571). By stabilizing the plasma membrane during the repetitive cycles of muscle contraction and relaxation, the DAPC prevents mechanical rupture and regulates localized signaling pathways essential for muscle health and vascular control. Mutations in the genes encoding DAPC components, particularly the DMD gene, result in the loss of the entire complex from the sarcolemma, leading to progressive muscle degeneration, fibrosis, and the clinical manifestations of Duchenne and Becker muscular dystrophies (NIH: GeneReviews). Therapeutic strategies targeting the DAPC focus on restoring the expression of functional dystrophin or stabilizing the complex through antisense oligonucleotide-mediated exon skipping, gene replacement therapy using micro-dystrophin, or small molecule read-through of nonsense mutations (FDA: Elevidys, Exondys 51). Additionally, stabilizing the DAPC is a key goal in treating various forms of limb-girdle muscular dystrophy where sarcoglycan or dystroglycan subunits are deficient (PubMed: 26897140).

Other names

Dystrophin-glycoprotein complexDGCDystrophin-associated glycoprotein complexDAGC

Restoration of dystrophin protein expression via antisense oligonucleotide-mediated exon skipping, gene replacement therapy using micro-dystrophin, or small molecule read-through of nonsense mutations to stabilize the DAPC at the sarcolemma.