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Brenman, JE, Chao, DS, Xia, H, Aldape, K and Bredt, DS (1995) Nitric oxide synthase complexed with dystrophin and absent from skeletal muscle sarcolemma in Duchenne muscular dystrophy. Cell 82:743-52
Nitric oxide (NO) is synthesized in skeletal muscle by neuronal-type NO synthase (nNOS), which is localized to sarcolemma of fast-twitch fibers. Synthesis of NO in active muscle opposes contractile force. We show that nNOS partitions with skeletal muscle membranes owing to association of nNOS with dystrophin, the protein mutated in Duchenne muscular dystrophy (DMD). The dystrophin complex interacts with an N-terminal domain of nNOS that contains a GLGF motif. mdx mice and humans with DMD evince a selective loss of nNOS protein and catalytic activity from muscle membranes, demonstrating a novel role for dystrophin in localizing a signaling enzyme to the myocyte sarcolemma. Aberrant regulation of nNOS may contribute to preferential degeneration of fast-twitch muscle fibers in DMD.
Amino Acid Oxidoreductases/analysis; Amino Acid Oxidoreductases/classification; Amino Acid Sequence; Animals; Cytoskeleton/chemistry; Cytosol/enzymology; Dystrophin/analysis; Humans; Immunohistochemistry; Isoenzymes/analysis; Mice; Mice, Inbred mdx; Molecular Sequence Data; Muscle, Skeletal/chemistry; Muscle, Skeletal/enzymology; Muscular Dystrophies/enzymology; Muscular Dystrophy, Animal/enzymology; Nitric Oxide Synthase; Sarcolemma/chemistry; Sarcolemma/enzymology
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