Dystrophin and Associated Muscle Proteins Kevin Cashman Biol. 317 March 22, 2006

Dystrophin A 427-kDa cytoskeletal protein and a member of the β- spectrin/α-actinin protein family Has an actin binding domain to bind to F-actin myofilaments Gene contains 79 exons in which with a high rate of alternate splicing on the C-terminus Associates with many other proteins to form the dystrophin glyco-protein complex (DGC)

List of Dystrophin Associated Proteins β-dystroglycan= sacrolemma spanning protein that dystrophin binds to F-actin= N-terminus of dystrophin binds to β-dystrobrevin= sacroplasmic protein that binds to dystrophin and the sarcoglycan complex Sarcoglycan complex= α,β,γ,δ-sarcoglycan proteins embedded into the sarcolemma that associates with β- dystrobrevin, and α and β-dystroglycan primarily.

List of Dystrophin Associated Proteins (cont.) α-dystroglycan= associates to β-dystroglycan and laminin-2 outside of the sacrolemma laminin-2= binds to the extracellular matrix and accociates with α-dystroglycan

Functions of DGC Two functions: To act as a shock-like complex to protect the muscle fiber’s sacrolemma from stress induced fractures during muscle contractions Associated proteins, nitric oxide synthase (NOS) and growth factor receptor bound protein 2 (GRB2), maintain cell viability and regulate the functions of the cytoskeleton.

Problems Mutations in the dystrophin gene can cause truncated proteins that get low productions levels, or the dystrophin protein isn’t produced at all. Without this the complex cannot bind to F-actin and fulfill its role. There are hundreds of mutations associated with the dystrophin gene in the majority of the exons and many of the mutations cause a type of dystrophy. Duchenne muscular dystrophy (absent) and Becker muscular dystrophy (truncated) are two of the most severe mutations.

References The Dystrophin Story, Function and Genetics of Dystrophin and Dystrophin-Related Proteins in Muscle, Blake et al (2002); Physiological Reviews, 82: au/DNA/images/dystrophin.gif&imgrefurl= DNA/SWISS- PROTdystrophin.htm&h=224&w=207&sz=13&tbnid=bIU8EqiYBpH9nM:&tbnh =102&tbnw=94&hl=en&start=5&prev=/images%3Fq%3DDystrophin%26svnu m%3D10%26hl%3Den%26lr%3D An Introduction to Human Molecular Genetics (2005), Jack Pasternak; Miley-Liss Inc., New Jersey.