dystrobrevins

Dystrobrevins are a family of cytoplasmic proteins that function as part of the dystrophin-associated protein complex (DAPC), a multi-protein assembly that links the cytoskeleton of muscle cells to the extracellular matrix. In muscle and certain brain cells, dystrobrevins help anchor cytoskeletal actin to the sarcolemma and participate in membrane stabilization during muscle contraction. They also act as adapters that recruit signaling proteins to the membrane.

The dystrobrevin family includes multiple isoforms, with alpha-dystrobrevin and beta-dystrobrevin as the major muscle-expressed forms. A gamma-dystrobrevin isoform has been described primarily in brain tissue. These proteins are produced by alternative splicing, yielding a range of isoforms with differing subcellular localization and interactions. All isoforms share conserved regions that mediate binding to dystrophin and to syntrophins, adapters that connect to other signaling and cytoskeletal components.

Functionally, dystrobrevins contribute to the assembly and stability of the DAPC at the sarcolemma, helping to maintain sarcolemmal integrity during contraction and to organize signaling modules at the membrane. By binding to dystrophin and syntrophins, they help recruit kinases and other signaling proteins to the complex, potentially influencing pathways relevant to muscle physiology.

Clinical relevance is primarily investigated in animal models. Mice lacking dystrobrevin show impaired DAPC assembly and muscle pathology, underscoring the role of this family in muscle membrane stabilization. In humans, alterations in dystrobrevin expression or splicing have been studied in the context of muscular dystrophy and related disorders; the exact contributions are still being clarified.