Disease relevance of Dtna

• Role for alpha-dystrobrevin in the pathogenesis of dystrophin-dependent muscular dystrophies [1].
• Here we show that mice deficient in alpha-dystrobrevin, a cytoplasmic protein of the DGC, exhibit skeletal and cardiac myopathies [1].
• In this study we investigated the feasibility of this method for extracting four surface glycoprotein antigens (87K, 95-150K, HLA-DR, and HLA-A,B,C) from cultured human melanoma cells [2].
• On the mdx background, the palmitoylated form of alpha-dystrobrevin was expressed on the sarcolemma but did not significantly ameliorate the muscular dystrophy phenotype [3].

High impact information on Dtna

• We have now found that by several criteria the 68K myristoylated protein is similar or identical to the 80/87K protein, a major specific substrate for protein kinase C (PKC) found in brain and fibroblasts (for review see refs 7,8) [4].
• Using knockout mice, we show that a cytoplasmic DGC component, alpha-dystrobrevin (alpha-DB), is dispensable for formation of the neuromuscular junction (NMJ) but required for maturation of its postsynaptic apparatus [5].
• Tyrosine-phosphorylated and nonphosphorylated isoforms of alpha-dystrobrevin: roles in skeletal muscle and its neuromuscular and myotendinous junctions [6].
• alpha-Dystrobrevin (DB), a cytoplasmic component of the dystrophin-glycoprotein complex, is found throughout the sarcolemma of muscle cells [6].
• Very recently, it was shown that gene knockout mice for a DAP, alpha-dystrobrevin, exhibit a dystrophic phenotype, possibly due to defects in muscle cell signaling [7].

Biological context of Dtna

• In addition to providing a membrane scaffold, members of the DPC such as the alpha-dystrobrevin protein family are thought to play an important role in intracellular signal transduction [8].
• Since inhibitors of tyrosine protein phosphorylation block acetylcholine receptor clustering in cultured muscle cells, we examined the role of alpha-dystrobrevin during synapse formation and in response to agrin [9].
• Given that the up-regulation of several genes has a beneficial effect on the muscle in some dystrophic mouse models, alpha-dystrobrevin has a number of properties that might be protective in muscular dystrophy [10].
• We show that the similarity between beta-dystrobrevin and alpha-dystrobrevin is reflected in the conservation of their exon-intron junctions. beta-Dystrobrevin has been localized to proximal mouse Chromosome (Chr) 12 by backcross mapping [11].
• A novel mechanism for modulating synaptic gene expression: differential localization of alpha-dystrobrevin transcripts in skeletal muscle [12].

Anatomical context of Dtna

• Dysbindin co-localizes with alpha-dystrobrevin at the sarcolemma and is up-regulated in dystrophin-deficient muscle [8].
• Using specific antibodies, we show that C2 myoblasts and early myotubes only produce alpha-dystrobrevin-1, the mammalian orthologue of Torpedo dystrobrevin, whereas mature skeletal muscle expresses three distinct alpha-dystrobrevin isoforms [9].
• Daily respiratory muscle training in mdx mice, induces a beneficial effect on diaphragm strength, with an over-expression of alpha-dystrobrevin [13].
• These data suggest that alpha-dystrobrevin provides a link between the dystrophin protein complex and the intermediate filament network at the neuromuscular junction, which may be important for the maintenance and maturation of the synapse [14].

Associations of Dtna with chemical compounds

• alpha-Dystrobrevin, the mammalian orthologue of the Torpedo 87-kDa postsynaptic protein, is a dystrophin-associated and dystrophin-related protein [15].

Physical interactions of Dtna

• A key component of the dystrophin protein complex is alpha-dystrobrevin, a dystrophin-associated protein whose absence results in neuromuscular junction defects and muscular dystrophy [14].

Other interactions of Dtna

• Skeletal muscles from Xenopus reveals the presence of two distinct beta-dystroglycan complexes, one with dystrophin and another one which involves alpha-dystrobrevin [16].
• However, EOM exhibited novel fiber-type-specific extrasynaptic localization of two key DGC signaling-related molecules: alpha-dystrobrevin 1 (global MIFs) and syntrophin beta1 (global MIFs and orbital MIFs and SIFs) [17].

Analytical, diagnostic and therapeutic context of Dtna

• This co-immunoprecipitation is dependent on the presence of alpha-dystrobrevin but not beta-dystrobrevin [18].

References