Disease relevance of DBN1

• Drebrin, a dendritic spine protein, is manifold decreased in brains of patients with Alzheimer's disease and Down syndrome [1].
• Reduced drebrin could be responsible for or representing the loss of spine plasticity in DS and may be a useful indicator for the impaired arborization in neurodegenerative disorders [1].
• Therefore, we have studied the organization of drebrin in motile cultured cells such as murine B16F1 melanoma and human SV80 fibroblast cells, using live cell confocal microscopy [2].
• In squamous cell carcinomas, keratoacanthomas, and in epidermal precancers, drebrin is heterogeneously distributed, appearing as mosaics [3].
• Here, we report on the presence of drebrin in normal human skin, epithelial skin cancers, and cultured keratinocytes [3].

Psychiatry related information on DBN1

• Immunocytochemical study demonstrated that widespread drebrin immunoreactivity was observed in hippocampal formations of control human brains, while Alzheimer's disease (AD) brains showed remarkable reductions in this immunoreactivity [4].
• Drebrin has been reported to be engaged in dendritic-cytoskeleton modulation at synapses, and such a novel NXF signaling system on neural gene promoter may be a molecular target of the adverse effects of Sim2 in the mental retardation of Down's syndrome [5].
• Alzheimer disease, the most common cause of dementia in the elderly, was associated with an additional 81% decrease in levels of drebrin, a protein regulating postsynaptic plasticity [6].

High impact information on DBN1

• Identification of a novel basic helix-loop-helix-PAS factor, NXF, reveals a Sim2 competitive, positive regulatory role in dendritic-cytoskeleton modulator drebrin gene expression [5].
• Expression of two developmentally regulated brain-specific proteins is correlated with late outgrowth of the pyramidal tract [7].
• Drebrin and mammalian Abp1 (mAbp1) are actin-binding proteins found previously to bind to Golgi membranes in an ARF1-dependent manner in vitro [8].
• The mechanisms for selective recruitment of mAbp1 and drebrin to Golgi membranes indicate how actin-based structures are able to select specific actin-binding proteins and, thus, carry out multiple different functions within cells [8].
• Despite sharing homology through two shared actin binding domains, drebrin and mAbp1 have different subcellular localization and bind to distinct actin structures on the Golgi apparatus [8].

Biological context of DBN1

• We conclude that these drebrin complexes and drebrin-rich structures allow the build-up and maintenance of high local drebrin concentrations in strategic positions for the regulation of actin filament assembly, thereby contributing to cell motility and morphology, in particular local changes of plasticity and the formation of protrusions [9].
• A full length cDNA clone of human drebrin E has been isolated from a cDNA library of human fetus brain [10].
• The deduced amino acid sequence, except for the internal 138-nucleotide sequence (ins2), exhibits 88% homology with rat drebrin A [10].
• Spot blot hybridization using flow-sorted human chromosomes provides evidence that the gene encoding human drebrin protein locates on human chromosome 5 [10].
• Drebrin has been known to act on actin filaments at dendritic spines to cause morphological change, and might be related to the plasticity of synaptic transmission [11].

Anatomical context of DBN1

• By contrast, the podocytes of rodent glomeruli appear to contain significant drebrin concentrations only during early developmental stages [12].
• Cell biological and biochemical characterization of drebrin complexes in mesangial cells and podocytes of renal glomeruli [12].
• Drebrin, located in the dendritic spines of the neuron, plays a role in the synaptic plasticity together with actin filaments [1].
• By double-label fluorescence microscopy we have found drebrin enriched in actin microfilament bundles associated with plaques of cell-cell contact sites representing adhering junctions [13].
• The occurrence and the possible functions of drebrin in non-neuronal cells, notably epithelial cells, and the significance of the existence of two different actin-anchoring junctional plaques is discussed [13].

Associations of DBN1 with chemical compounds

• In biochemical analyses of various cells and tissues, employing gel filtration, sucrose gradient centrifugation, immunoprecipitation and -blotting, we have identified distinct states of soluble drebrin: a approximately 4S monomer, an 8S, ca. 217-kDa putative trimer, a 13S and a > 20S oligomer [9].
• The Actin-depolymerizing Factor Homology and Charged/Helical Domains of Drebrin and mAbp1 Direct Membrane Binding and Localization via Distinct Interactions with Actin [8].
• Activation of N-methyl-D-aspartate receptor induces a shift of drebrin distribution: disappearance from dendritic spines and appearance in dendritic shafts [14].
• In the present in vitro study, we examined whether glutamate stimulation alters drebrin content in dendritic spines [14].
• In parallel with the neuronal differentiation following retinoic acid treatment, drebrin E was accumulated, accompanying filamentous (F) actin, in the submembranous cortical cytoplasm [15].

Regulatory relationships of DBN1

• The glutamate-induced shift of drebrin immunostaining was blocked by an NMDA receptor antagonist [14].

Other interactions of DBN1

• Interactions of drebrin and gephyrin with profilin [16].
• Decreased drebrin could not simply be due to cell loss (F-actin) or neuronal loss (comparable neuron-specific enolase between groups) [1].
• Furthermore, decreased moesin is the second F-actin bundling protein, besides drebrin, that is manifold reduced in fetal DS brain [17].
• We conclude that at the time point of about 19 weeks of gestation (early second trimester) no neuronal loss can be detected but drebrin, a marker for dendritic spines and synaptosomal associated proteins alpha SNAP and SNAP 25 were significantly reduced indicating impaired synaptogenesis [18].
• In both the CD1 control animals and the S100B animals, the immunoreactivity of drebrin increased with age, however there were no significant between group differences [19].

Analytical, diagnostic and therapeutic context of DBN1

• In adult human and bovine kidneys, drebrin is, in addition, markedly enriched in the foot processes of podocytes, as also demonstrable by immunoelectron microscopy [12].
• Immunohistochemistry and double-label confocal laser scanning microscopy have shown intense drebrin reactions in the mesangial cells of diverse mammalian species [12].
• Western blot analysis demonstrated that drebrin E (116kD) as well as drebrin A (125 kD) presented in adult human brains, and that these isoforms were decreased in parallel in AD brains [4].
• Molecular cloning of cDNA encoding human drebrin E and chromosomal mapping of its gene [10].
• Drebrin expression is increased in spinal motoneurons of rats after axotomy [11].

References