Disease relevance of Dtnb

• A database search revealed that two mouse genetic diseases involving tissues expressing beta-dystrobrevin have been mapped to this region, namely, congenital polycystic kidneys (cpk) and fatty liver dystrophy (fld) [1].

High impact information on Dtnb

• In common with dystrophin, beta-dystrobrevin is found in neurons of the cortex and hippocampal formation but is not found in the brain microvasculature [2].
• In addition, the levels of several beta-dystrobrevin-interacting proteins, namely Dp71 isoforms and the syntrophins, were greatly reduced from the basal membranes of kidney tubules and liver sinusoids and on Western blots of crude kidney and liver microsomes of beta-dystrobrevin-deficient mice [3].
• Dystrobrevins are now thought to play an important role in intracellular signal transduction, in addition to providing a membrane scaffold in muscle, but the precise role of beta-dystrobrevin has not yet been determined [4].
• These complexes can be broadly grouped according to their dystrobrevin content: beta-dystrobrevin containing complexes are present at the basal region of renal epithelial cells, whilst alpha-dystrobrevin-1 containing complexes are found in endothelial and smooth muscle cells [5].
• In the present study, we assessed the kinetics of the dystrobrevin-Kif5A interaction by quantitative pull-down assay and surface plasmon resonance (SPR) analysis and found that beta-dystrobrevin binds to kinesin with high affinity (K(D) approximately 40 nM) [6].

Biological context of Dtnb

• The mouse beta-dystrobrevin gene is organized into 21 exons spanning over 130 kb of DNA [1].
• 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 [1].
• In order to understand if structural changes induced by post-translational modifications could affect dystrobrevin affinity for kinesin, we phosphorylated beta-dystrobrevin in vitro and found that it showed reduced binding capacity towards kinesin [6].
• Genes involved in bioenergetic homeostasis, such as the mitochondrial creatine kinase and the gamma subunit of ATP synthase were also found to be abnormally expressed, while expression of the structural proteins beta-dystrobrevin and rapsyn was also significantly affected [7].

Anatomical context of Dtnb

• Dialysis of myocytes with GSH (5 mM) or DTT (5 mM) prevented suppression of Ito by H2O2 and DTNB but did not alter the effects of NH2Cl or Ch-T on either Idr or Ito [8].
• The effects of reduction by DTT, oxidation by DTNB and treatment with NEM on the thiol contents and insulin binding to its receptor in mice liver membranes were studied [9].

Associations of Dtnb with chemical compounds

• Sequence analysis indicates that this gene, named DTN-B, is highly homologous to the rabbit A0, the previously described dystrobrevin (DTN), Torpedo 87 kDa and to the C-terminus of dystrophin [10].
• Finally, DTT pretreatment enhanced the long lasting allodynia induced by i.t. administration of dynorphin, whereas post-treatment with DTNB reduced the permanent allodynia induced by dynorphin for 5 days [11].
• The dibasic cleaving enzyme was completely inhibited in the presence of 20-50 mM amine buffers, 0.1 mM EDTA, 0.5 mM 1,10-phenanthroline, 0.5 mM N-ethylmaleimide, and 1mM DTNB [12].
• Intrathecal (i.t.) administration of DTT (0.1-30 nmol), presumably reducing the NMDA receptor, dose-dependently enhanced NMDA-induced nociceptive behaviors, and this enhancement was blocked by the oxidizing agent, DTNB [11].
• Arsenicals and arsinothiols, complexes of As(III)-containing compounds with L-cysteine or glutathione, were tested as inhibitors of the DTNB reductase activity of the purified enzyme [13].

Analytical, diagnostic and therapeutic context of Dtnb

• Co-immunoprecipitation with a monoclonal kinesin heavy chain antibody precipitated both alpha- and beta-dystrobrevin, indicating that this interaction is not restricted to the beta-dystrobrevin isoform [4].
• Pull-down and immunofluorescence experiments also showed a direct interaction between beta-dystrobrevin and Kif5B [4].
• No beta-dystrobrevin was detected in these mice by Western blotting or immunocytochemistry [3].
• During pH titration and DTNB reaction, MT-4 and MT-1 exhibit comparable behavior [14].

References