Disease relevance of UTRN

• However, while dystrophin is absent or severely reduced in Duchenne/Becker muscular dystrophy, DRP continues to be expressed [1].
• A key component of the dystrophin-associated protein complex (DPC) is alpha-dystrobrevin, a dystrophin-related and -associated protein whose absence results in muscular dystrophy and neuromuscular junction defects [1,2] [2].
• The molecular stimulus for the marked upregulation of DRP in DMD/BMD and in the inflammatory myopathies is not known [3].
• In Duchenne/Becker dystrophy (DMD/BMD) and in polymyositis (PM) or dermatomyositis (DM) DRP was present throughout the extrajunctional surface membrane of extra- and intrafusal muscle fibers, particularly regenerating ones [3].
• After subcellular fractionation of BC3H1 or glioma cells, nearly all of the utrophin was found in the Triton-soluble fraction, suggesting an association with cell membranes [4].

Psychiatry related information on UTRN

• CONCLUSIONS: Two DRPs, needs additional drug therapy and wrong drug, are associated with reduced self-reported physical health in arthritis and low back pain, while the DRP needs additional drug therapy is also associated with reduced self-reported mental health [5].
• All subjects were interviewed by psychiatrists and were administered psychological tests such as SAS (self-rating anxiety scale), SDS (self-rating depression scale), POMS (Profile of Mood States), HADS (Hospital Anxiety and Depression Scale) and DRP (Depression-related personality traits) [6].

High impact information on UTRN

• Dystrophin is also the prototype of a family of dystrophin-related proteins, many of which are found in muscle [7].
• This family includes utrophin and alpha-dystrobrevin, which are involved in the maintenance of the neuromuscular junction architecture and in muscle homeostasis [7].
• A role for dystrophin-associated glycoproteins and utrophin in agrin-induced AChR clustering [8].
• A five-day course of erythromycin or tetracycline, administered after a base-line period of 10 to 17 days, markedly reduced or eliminated DRP excretion in urine and stool [9].
• The dystrophin-related sequence identifies a 13-kb transcript in human fetal muscle and maps to chromosome 6 [10].

Chemical compound and disease context of UTRN

• Utrophin, the autosomal dystrophin-related protein (DRP), is expressed in HeLa cells, smooth muscle-like BC3H1 cells from mouse brain, COS monkey kidney cells, the P388D1 monocyte-macrophage cell line and untransformed human skin fibroblasts, as well as in rat C6 glioma and Schwannoma cells [4].
• Strongly positive immunoreaction to DRP at the neuromuscular junctions in all biopsied specimens and faint reaction on the surface membrane of atrophic fibers in amyotrophic lateral sclerosis suggest that DRP is an anchor protein of the acetylcholine receptor [11].
• CONCLUSION: These results suggest that attenuation in calpain-induced degradation of DRP complex is a possible mechanism for the Tra- or Can-mediated improvement of the pathogenesis of CHF following myocardial infarction [12].

Biological context of UTRN

• Function and genetics of dystrophin and dystrophin-related proteins in muscle [7].
• The subcellular distribution of chromosome 6-encoded dystrophin-related protein in the brain [1].
• Utrophin is encoded by multiple small exons spanning approximately 900 kb [13].
• We have constructed a 1.25 Mb contig of eight yeast artificial chromosome (YAC) clones covering the utrophin gene located on chromosome 6q24 [13].
• The importance of using protein-specific antibodies for dystrophin analysis has been underscored by the identification of a protein, designated utrophin, which exhibits significant sequence homology with dystrophin [14].

Anatomical context of UTRN

• The expression of DMDL protein is not restricted to smooth and skeletal muscle, however, since relatively large amounts are present in transformed brain cell lines of both glial and Schwann cell origin [15].
• The DMDL protein was undetectable in the nonjunctional sarcolemma of normal human muscle, but was observed in nonjunctional sarcolemma of Duchenne muscular dystrophy patients, where dystrophin itself is absent or greatly reduced [15].
• Localization of the DMDL gene-encoded dystrophin-related protein using a panel of nineteen monoclonal antibodies: presence at neuromuscular junctions, in the sarcolemma of dystrophic skeletal muscle, in vascular and other smooth muscles, and in proliferating brain cell lines [15].
• Within the parenchyma proper, DRP is located at the inner plasma face of astrocytic foot processes at the abluminal aspect of the blood-brain barrier [1].
• DRP is enriched in the choroid plexus, pia mater, intracerebral vasculature, and ependymal lining [1].

Associations of UTRN with chemical compounds

• These antibodies provide direct evidence that DMDL protein is localized near acetylcholine receptors at neuromuscular junctions in normal and mdx mouse intercostal muscle [15].
• Initial studies in the electric organ of Torpedo californica showed that the dystrophin-related protein dystrobrevin (87K) co-purifies with the acetylcholine receptors and other postsynaptic proteins [16].
• We confirmed these findings and extended them to show that the utrophin content of control and dexamethasone-treated normal myotube cultures is not significantly different [17].
• Assembly is characterized by coalescence of sulfatide, DG, and c-Src into a Lm-associated complex; by DG-dependent recruitment of utrophin and Src activation; and by integrin-dependent focal adhesion kinase phosphorylation [18].
• In extracts from cells treated with peroxyvanadate, where endogenous (beta)-dystroglycan was tyrosine phosphorylated, (beta)-dystroglycan was no longer co-immunoprecipitated with utrophin fusion constructs [19].

Physical interactions of UTRN

• Utrophin lacks the rod domain actin binding activity of dystrophin [20].
• The carboxyterminus of the ATP-binding cassette transporter A1 interacts with a beta2-syntrophin/utrophin complex [21].
• By contrast, panning with an extended region containing the WW, EF hands, and ZZ domain defines the consensus binding motif, PPxY which is also found in beta-dystroglycan, a component of the DAP complex that interacts with utrophin in several tissues [22].
• Binding of its cytoplasmic tail to beta2-syntrophin suggests that ICA512 connects secretory granules to the utrophin complex and the actin cytoskeleton [23].
• OBJECTIVES: Genetic depletion of dystrophin-related protein (DRP) complex causes cardiomyopathy in animals and humans [12].

Enzymatic interactions of UTRN

• Immunoprecipitation studies demonstrated that MARCH-V interacts with mitofusin 2 (MFN2) and ubiquitinated forms of Drp1 [24].

Regulatory relationships of UTRN

• Utrophin is therefore expressed in the presence and absence of dystrophin and down-regulated before birth in normal fetal muscle fibres [25].

Other interactions of UTRN

• The cardiac expression of the dystrophin related protein utrophin was increased, and the 43 kDa (beta-dystroglycan), 50 kDa (alpha-sarcoglycan) and 59 kDa (syntrophin) dystrophin associated proteins (DAPs) were co-isolated and present in nearly normal amounts in the membrane [26].
• The staining intensities of utrophin, vimentin and desmin were also higher in small regenerating fibers [27].
• We found no correlation between utrophin expression and DAP expression [28].
• Here, we present the 2.0 A structure of the second calponin homology domain of utrophin solved by X-ray crystallography, and compare it to the other calponin homology domains previously determined from spectrin and fimbrin [29].
• In Becker dystrophy, 43DAG expression was more extensive around individual fibres, showed more interfibre variation and was more closely related to the intensity of immunolabelling for both dystrophin and utrophin than in Duchenne dystrophy [30].
• Laser-capture microscopy of tibialis anterior NMJ and extrasynaptic transcriptomes and gene transfer studies provide spatial and direct evidence, respectively, for ERF-mediated utrophin repression in vivo [31].

Analytical, diagnostic and therapeutic context of UTRN

• Sequence analysis of the entire cDNA for the autosomal dystrophin-related protein utrophin has shown that dystrophin and utrophin are closely related [32].
• A dystrophin-related protein (DRP) encoded by a gene on chromosome 6 was studied in 14 normal and 79 pathological human skeletal muscle biopsies, as well as in cultured myotubes by light microscopic immunocytochemistry and quantitative immunoblots [3].
• On Western blots, utrophin was shown to have a smaller relative molecular mass than adult dystrophin, but similar to the fetal isoform [25].
• To determine the utility of dystrophin and utrophin staining in the differential diagnosis of childhood muscular dystrophy [33].
• Using maltose binding protein fusion constructs to the carboxy-terminal domains of utrophin we were able to demonstrate specific interactions between the WW, EF and ZZ domains of utrophin and (beta)-dystroglycan by co-immunoprecipitation with endogenous (beta)-dystroglycan [19].

References