title: Nonmechanical Roles of Dystrophin and Associated Proteins in Exercise, Neuromuscular Junctions, and Brains.
abstract: Dystrophin-glycoprotein complex (DGC) is an important structural unit in skeletal muscle that connects the cytoskeleton (f-actin) of a muscle fiber to the extracellular matrix (ECM). Several muscular dystrophies, such as Duchenne muscular dystrophy, Becker muscular dystrophy, congenital muscular dystrophies (dystroglycanopathies), and limb-girdle muscular dystrophies (sarcoglycanopathies), are caused by mutations in the different DGC components. Although many early studies indicated DGC plays a crucial mechanical role in maintaining the structural integrity of skeletal muscle, recent studies identified novel roles of DGC. Beyond a mechanical role, these DGC members play important signaling roles and act as a scaffold for various signaling pathways. For example, neuronal nitric oxide synthase (nNOS), which is localized at the muscle membrane by DGC members (dystrophin and syntrophins), plays an important role in the regulation of the blood flow during exercise. DGC also plays important roles at the neuromuscular junction (NMJ) and in the brain. In this review, we will focus on recently identified roles of DGC particularly in exercise and the brain.
authors.affiliation: Department of Medical Genetics, University of Alberta Faculty of Medicine and Dentistry. bmiskew@ualberta.ca.
authors.forename: Bailey
authors.initials: B
authors.lastname: Nichols
authors.affiliation: Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawa-higashi, Kodaira, Tokyo 187-8502, Japan. takeda@ncnp.gp.jp.
authors.forename: Shin'ichi
authors.initials: S
authors.lastname: Takeda
authors.affiliation: Department of Medical Genetics, University of Alberta Faculty of Medicine and Dentistry. toshifum@ualberta.ca.|Muscular Dystrophy Canada Research Chair, 8812-112 St, Edmonton, AB T6G 2H7, Canada. toshifum@ualberta.ca.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Yokota
keywords: brain; dystrophin; dystrophin-glycoprotein complex (DGC); exercise; muscular dystrophy; neuronal nitric oxide synthase (nNOS); sildenafil citrate (Viagra®); syntrophin; tadalafil (Cialis®); two-hit hypothesis (two-hit theory)