Controversies about the function of dystrophin in muscle.
Dystrophin, a product of a gene located at the chromosome Xp21 locus, is a cytoskeletal protein expressed in skeletal, cardiac and smooth muscles, and in the brain, and is located on the inner site of the plasma membrane. Dystrophin in the skeletal muscles is absent or appears only in traces in Duchenne dystrophy, it is reduced with normal/changed molecular weight in Becker dystrophy and it is absent/reduced in mdx mice. It is supposed that dystrophin acts either as a structural scaffold that supports mechanical stress in sarcolemma, or participates in regulating intracellular Ca2+ level. There are also data indicating that dystrophin takes part in force and signal transduction processes, in the aggregation of neurotransmitter receptors, and prevents an excessive generation of reactive oxygen free radical species. The main hypotheses indicate that lack of structural support, an excessive influx of Ca2+ ions into the muscle cell, or a combination of both these mechanisms in dystrophin-deficient muscle fibres, is responsible for muscle pathology in progressive muscular dystrophy. There are arguments supporting these hypotheses. There are, however, also data indicating that the presented arguments are doubtful. Despite recent advances in the knowledge of the pathogenesis of muscular dystrophies and the advent of modern techniques, we are still very far away from understanding what is the real function of dystrophin in muscle.
Niebroj-Dobosz
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Department of Neurology, Medical University, Warszawa, Poland.
Fidziańska
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Hausmanowa-Petrusewicz
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D000818:Animals; D016189:Dystrophin / Q000502:physiology*; D006801:Humans; D009137:Muscular Dystrophy, Animal / Q000473:pathology / Q000503:physiopathology*; D020388:Muscular Dystrophy, Duchenne / Q000473:pathology / Q000503:physiopathology*
D016189:Dystrophin