Dystrophin and Associated Muscle Proteins Kevin Cashman Biol. 317 March 22, 2006.
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Transcript of Dystrophin and Associated Muscle Proteins Kevin Cashman Biol. 317 March 22, 2006.
![Page 1: Dystrophin and Associated Muscle Proteins Kevin Cashman Biol. 317 March 22, 2006.](https://reader031.fdocument.pub/reader031/viewer/2022032202/56649da05503460f94a8c0ec/html5/thumbnails/1.jpg)
Dystrophin and Associated Muscle Proteins
Kevin Cashman
Biol. 317
March 22, 2006
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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)
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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.
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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
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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.
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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.
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References
The Dystrophin Story, http://compbio.berkeley.edu/people/ed/rust/Dystrophin.html
Function and Genetics of Dystrophin and Dystrophin-Related Proteins in Muscle, Blake et al (2002); Physiological Reviews, 82: 291-329.
http://www.mja.com.au/public/issues/179_09_031103/byr10494_fm-1.gif
http://images.google.com/imgres?imgurl=http://embryology.med.unsw.edu.au/DNA/images/dystrophin.gif&imgrefurl=http://embryology.med.unsw.edu.au/DNA/SWISS-PROTdystrophin.htm&h=224&w=207&sz=13&tbnid=bIU8EqiYBpH9nM:&tbnh=102&tbnw=94&hl=en&start=5&prev=/images%3Fq%3DDystrophin%26svnum%3D10%26hl%3Den%26lr%3D
An Introduction to Human Molecular Genetics (2005), Jack Pasternak; Miley-Liss Inc., New Jersey.