Disease relevance of Dbn1

• Reduced drebrin has been found in the brain of patients with Alzheimer's disease or Down's syndrome [1].
• To examine whether the down-regulation of drebrin protein levels causes deficits in higher brain function, such as memory or cognition, we performed antisense-induced knockdown of drebrin A expression in rat brain using an hemagglutinating virus of Japan (HVJ)-liposome gene transfer technique [1].

Psychiatry related information on Dbn1

• We investigated the effects of drebrin in vivo knockdown on spatial memory in a water-maze task, sensorimotor gating in a pre-pulse-inhibition test, adaptive behaviors in an open-field test, and sensitivity to psychostimulant in an amphetamine-induced locomotor response [1].
• Rats with drebrin A in vivo knockdown displayed a stronger preference for a previous event due to perseverative behavior, impaired pre-pulse inhibition (PPI), increased locomotor activity, anxiety-like behavior, and an increased sensitivity to psychostimulant, suggesting behaviors related to schizophrenia [1].

High impact information on Dbn1

• In vitro, drebrin reduced the sliding velocity of actin filaments on immobilized myosin and inhibited the actin-activated ATPase activity of myosin [2].
• Modulatory role of drebrin on the cytoskeleton within dendritic spines in the rat cerebral cortex [2].
• Drebrin, actin, myosin, and gelsolin were co-precipitated [2].
• We found that adult-type drebrin is localized in the dendritic spines of rat forebrain neurons, where it binds to the cytoskeleton [2].
• Although the actin-binding proteins mAbp1 (SH3p7) and drebrin share sequence homology, they are differentially segregated into two distinct ARF-dependent actin complexes [3].

Biological context of Dbn1

• Drebrin A is a neuron-specific F-actin binding protein, and plays a pivotal role in the spine formation [4].
• Gene transfection experiments revealed that tropomyosin was dissociated from actin filaments in drebrin-overexpressing fibroblasts [5].
• Following treatment with colcemid (5 micrograms/ml) and cytochalasin D (0.5 micrograms/ml), most L cells collapsed into round cells, while drebrin expressing cells were resistant to the treatment, keeping their cell shapes [6].
• Up-regulation of microtubule-associated protein 4 and drebrin A mRNA expression by antidepressants in rat hippocampus following chronic stress [7].
• Together, these data suggest that synaptic clustering of drebrin is an essential step for spine morphogenesis [8].

Anatomical context of Dbn1

• These results demonstrate that drebrin A accumulates spine-resident proteins via protein-protein interaction in filopodia, and suggest that the spine formation requires the concurrence of the increase of drebrin-A expression and the functional presynaptic contact [9].
• In this study, we expressed drebrin A tagged with green fluorescent protein (GFP-DA) in hippocampal neurons at 7-9 days in vitro when presynaptic terminals are not fully maturated [4].
• Here we examine the molecular mechanisms responsible for the changes in spine morphology, focusing on drebrin, an actin-binding protein that is known to change the properties of actin filaments [2].
• Drebrin is a development-associated neuroprotein whose cDNA into fibroblasts causes the formation of dendrite-like structures (Shirao, T., Kojima, N., and Obata, K. (1992) Neuroreport 3, 109-112) [5].
• Inhibition by drebrin of the actin-bundling activity of brain fascin, a protein localized in filopodia of growth cones [10].

Associations of Dbn1 with chemical compounds

• In adulthood, nearly all of the synaptic drebrin A is within spines forming asymmetric excitatory synapses, verified by gamma-aminobutyric acid (GABA) negativity [11].
• This result suggests that MAP-4 and drebrin may be involved in the antidepressant like effects of desipramine and fluoxetine [7].

Physical interactions of Dbn1

• Thus we hypothesize that drebrin may destabilize actin filaments by dissociating tropomyosin and alpha-actinin from actin filaments, resulting in the formation of axon and dendrites during neuronal development [5].

Regulatory relationships of Dbn1

• Overexpression of drebrin A in immature neurons induces the accumulation of F-actin and PSD-95 into dendritic filopodia, and the formation of large abnormal protrusions [9].

Other interactions of Dbn1

• In contrast, no changes occurred during the course of IH exposures in the expression of the synaptic proteins synaptophysin, SNAP25, and drebrin [12].
• The adult-type isoform of drebrin was detected by Western blotting after seventh day in primary cultured cortical neurons and the expression was coincidental with that of synaptophysin [13].
• These data indicated that the synaptic clustering of drebrin is necessary for that of PSD-95 in developing neurons [8].

Analytical, diagnostic and therapeutic context of Dbn1

• To identify the cytoskeletal proteins that associated with drebrin, we isolated drebrin-containing cytoskeletons using immunoprecipitation with a drebrin antibody [2].
• Fascin caused formation of actin bundles, a process that was inhibited in the presence of drebrin, as confirmed by electron microscopy and a low-speed centrifugation assay [10].
• During the purification of drebrin, we found that an actin-binding protein of 54 kDa was also expressed at high levels in embryonic brain, and this protein was identified by immunoblotting as fascin [10].
• Western blotting showed that drebrin A emerges at postnatal day (PNd) 6 and becomes progressively more associated with F-actin in the pellet fraction [11].

References