Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutations in dystrophin cause muscular dystrophy but also affect the CNS, including information processing in the retina. To better understand the molecular basis of these CNS deficits, we analyzed the molecular composition and developmental appearance of dystrophin and of the dystrophin-associated protein complex (DPC) in the embryonic and adult avian retina. We detected a concentration of the DPC at the vitreal border and in the outer plexiform layer of the adult retina. At both locations the complex had a different molecular composition and different developmental expression pattern. At the vitreal border, the complex was composed of utrophin, alpha-dystrobrevin-1, and dystroglycan, and was present at all stages of retinal development even before neurogenesis and gliogenesis. On the other hand, the complex in the outer plexiform layer consisted of dystrophin, beta-dystrobrevin and dystroglycan. The distribution of this complex changed from a diffusely distributed to an aggregated form during development concomitant with synapse formation in the outer plexiform layer. Solubilization of the retinal extracellular matrix by intravitreal injection of collagenase resulted in a redistribution of the complex at the retinal vitreal border but had no influence on the distribution of the dystrophin-associated proteins in the outer plexiform layer. These results demonstrate two types of dystrophin-like complexes in the chick retina with differential molecular compositions, different anchorage to the extracellular matrix, and different developmental expression patterns, suggesting distinct functions for the DPC at both locations.
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PMID:Molecular diversity of the dystrophin-like protein complex in the developing and adult avian retina. 1198 13

The dystrophin-associated protein complex (DPC), comprising sarcoglycans, dystroglycans, dystrobrevins, and syntrophins, is a component of synapses both in muscle and brain. Dysbindin is a novel component of the DPC, which binds to beta-dystrobrevin and may serve as an adaptor protein that links the DPC to an intracellular signaling cascade. Disruption of the DPC results in muscular dystrophy, and mutations in the human ortholog of dysbindin have been implicated in the pathogenesis of schizophrenia. In both cases, patients also present with neurological symptoms reminiscent of cerebellar problems. In the mouse cerebellum, dysbindin immunoreactivity is expressed at high levels in a subset of mossy fiber synaptic glomeruli in the granular layer. Lower levels of dysbindin immunoreactivity are also detected in Purkinje cell dendrites. In the cerebellar vermis, dysbindin-immunoreactive glomeruli are restricted to an array of parasagittal stripes that bears a consistent relationship to Purkinje cell parasagittal band boundaries as defined by the expression of the respiratory isoenzyme zebrin II/aldolase c. In a mouse model of Duchenne muscular dystrophy, the mdx mutant, in which dystrophin is not expressed, there is a dramatic increase in the number of dysbindin-immunoreactive glomeruli in the posterior cerebellar vermis. Moreover, the topography of the terminal fields is disrupted, replacing the stripes by a homogeneous distribution. Abnormal synaptic organization in the cerebellum may contribute to the neurological problems associated with muscular dystrophy and schizophrenia.
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PMID:Abnormal dysbindin expression in cerebellar mossy fiber synapses in the mdx mouse model of Duchenne muscular dystrophy. 1287 99

Mice rendered null for alpha-dystrobrevin, a component of the dystrophin complex, have muscular dystrophy, despite the fact that the sarcolemma remains relatively intact (Grady, R. M., Grange, R. W., Lau, K. S., Maimone, M. M., Nichol, M. C., Stull, J. T., and Sanes, J. R. (1999) Nat. Cell Biol. 1, 215-220) Thus, alpha-dystrobrevin may serve a signaling function that is important for the maintenance of muscle integrity. We have identified a new dystrobrevin-associated protein, DAMAGE, that may play a signaling role in brain, muscle, and peripheral nerve. In humans, DAMAGE is encoded by an intronless gene located at chromosome Xq13.1, a locus that contains genes involved in mental retardation. DAMAGE associates directly with alpha-dystrobrevin, as shown by yeast two-hybrid, and co-immunoprecipitates with the dystrobrevin-syntrophin complex from brain. This co-immunoprecipitation is dependent on the presence of alpha-dystrobrevin but not beta-dystrobrevin. The DAMAGE protein contains a potential nuclear localization signal, 30 12-amino acid repeats, and two MAGE homology domains. The domain structure of DAMAGE is similar to that of NRAGE, a MAGE protein that mediates p75 neurotrophin receptor signaling and neuronal apoptosis (Salehi, A. H., Roux, P. P., Kubu, C. J., Zeindler, C., Bhakar, A., Tannis, L. L., Verdi, J. M., and Barker, P. A. (2000) Neuron 27, 279-288). DAMAGE is highly expressed in brain and is present in the cell bodies and dendrites of hippocampal and Purkinje neurons. In skeletal muscle, DAMAGE is at the postsynaptic membrane and is associated with a subset of myonuclei. DAMAGE is also expressed in peripheral nerve, where it localizes along with other members of the dystrophin complex to the perineurium and myelin. These results expand the role of dystrobrevin and the dystrophin complex in membrane signaling and disease.
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PMID:DAMAGE, a novel alpha-dystrobrevin-associated MAGE protein in dystrophin complexes. 1462 85