The dystrophin–glycoprotein complex, cellular signaling, and the regulation of cell survival in the muscular dystrophies
Tóm tắt
Mutations of different components of the dystrophin–glycoprotein complex (DGC) cause muscular dystrophies that vary in terms of severity, age of onset, and selective involvement of muscle groups. Although the primary pathogenetic processes in the muscular dystrophies have clearly been identified as apoptotic and necrotic muscle cell death, the pathogenetic mechanisms that lead to cell death remain to be determined. Studies of components of the DGC in muscle and in nonmuscle tissues have revealed that the DGC is undoubtedly a multifunctional complex and a highly dynamic structure, in contrast to the unidimensional concept of the DGC as a mechanical component in the cell. Analysis of the DGC reveals compelling analogies to two other membrane‐associated protein complexes, namely integrins and caveolins. Each of these complexes mediates signal transduction cascades in the cell, and disruption of each complex causes muscular dystrophies. The signal transduction cascades associated with the DGC, like those associated with integrins and caveolins, play important roles in cell survival signaling, cellular defense mechanisms, and regulation of the balance between cell survival and cell death. This review focuses on the functional components of the DGC, highlighting the evidence of their participation in cellular signaling processes important for cell survival. Elucidating the link between these functional components and the pathogenetic processes leading to cell death is the foremost challenge to understanding the mechanisms of disease expression in the muscular dystrophies due to defects in the DGC. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 1575–1594, 2001
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Tài liệu tham khảo
Bonilla E, 1981, Freeze‐fracture studies of muscle caveolae in human muscular dystrophy, Am J Pathol, 104, 167
Brewster B, 1998, Neuromuscular disorders: clinical and molecular genetics, 323
Brown SC, 1999, Dystrophic phenotype induced in vitro by antibody blockade of muscle α‐dystroglycan–laminin interaction, J Cell Sci, 112, 209, 10.1242/jcs.112.2.209
Cary LA, 1999, Integrin‐mediated signal transduction pathways, Histol Histopathol, 14, 1001
DisatnikM‐H Mochly‐RosenD RandoTA.Essential role of ϵPKC in integrin‐mediated muscle cell spreading. Submitted.
Doctor RB, 1997, Loss of plasma membrane structural support in ATP‐depleted renal epithelia, Am J Physiol, 272, C439, 10.1152/ajpcell.1997.272.2.C439
Dubowitz V, 2000, What is muscular dystrophy? Forty years of progressive ignorance, J R Coll Phys Lond, 34, 464
Emery AEH, 1993, Duchenne muscular dystrophy
GalbiatiF EngelmanJA VolonteD ZhangXL MinettiC LiM HouH KneitzB EdelmannW LisantiMP.Caveolin‐3 null mice show a loss of caveolae changes in the microdomain distribution of the dystrophin–glycoprotein complex and T‐tubule abnormalities. J Biol Chem (in press).
Grozdanovic Z, 1999, Nitric oxide synthase in skeletal muscle fibers: a signaling component of the dystrophin–glycoprotein complex, Histol Histopathol, 14, 243
Henry MD, 2001, Distinct roles for dystroglycan, β1 integrin and perlecan in cell surface laminin organization, J Cell Sci, 114, 1137, 10.1242/jcs.114.6.1137
Jacobson C, 1998, α‐Dystroglycan functions in acetylcholine receptor aggregation but is not a coreceptor for agrin‐MuSK signaling, J Neurosci, 18, 6340, 10.1523/JNEUROSCI.18-16-06340.1998
James M, 2000, Adhesion‐dependent tyrosine phosphorylation of β‐dystroglycan regulates its interaction with utrophin, J Cell Sci, 113, 1717, 10.1242/jcs.113.10.1717
Koenig M, 1989, The molecular basis for Duchenne versus Becker muscular dystrophy: correlation of severity with type of deletion, Am J Hum Genet, 45, 498
Kramarcy NR, 1994, Association of utrophin and multiple dystrophin short forms with the mammalian Mr 58,000 dystrophin‐associated protein (syntrophin), J Biol Chem, 269, 2870, 10.1016/S0021-9258(17)42023-0
Kristensen SR, 1994, Mechanisms of cell damage and enzyme release, Dan Med Bull, 41, 423
Milner RE, 1993, Phosphorylation of dystrophin. The carboxyl‐terminal region of dystrophin is a substrate for in vitro phosphorylation by p34cdc2 protein kinase, J Biol Chem, 268, 21901, 10.1016/S0021-9258(20)80626-7
Padberg GW, 1998, Neuromuscular disorders: clinical and molecular genetics, 105
RandoTA.The role of nitric oxide in the pathogenesis of muscular dystrophies: a “two hit” hypothesis of the cause of muscle necrosis. Microsc Res Techn 2001;55 (in press).
Shemanko CS, 1995, Phosphorylation of the carboxyl terminal region of dystrophin by mitogen‐activated protein (MAP) kinase, Mol Cell Biochem, 152, 63, 10.1007/BF01076464
Tidball JG, 1995, Apoptosis precedes necrosis of dystrophin‐deficient muscle, J Cell Sci, 108, 2197, 10.1242/jcs.108.6.2197
Tome FMS, 1998, Neuromuscular disorders: clinical and molecular genetics, 21
Yang JT, 1993, Embryonic mesodermal defects in α5 integrin‐deficient mice, Development, 119, 1093, 10.1242/dev.119.4.1093