Disease relevance of Dbn1

• Using a drebrin-specific monoclonal antibody, we were able to detect drebrin protein in several different cell lines derived from fibroblasts, astrocytomas, and simple epithelia, but not in cell lines derived from stratified epithelia [1].
• Ultrastructural changes associated with neurite formation were examined in suitably cultured neuroblastoma cells (Neuro-2a) and drebrin (developmentally regulated brain protein) gene-transfected fibroblasts (L cells) in culture [2].

Psychiatry related information on Dbn1

• Drebrin had previously been described as an actin binding protein that diminishes in brains during Alzheimer's disease [3].

High impact information on Dbn1

• Drebrin is a novel connexin-43 binding partner that links gap junctions to the submembrane cytoskeleton [3].
• The rearrangement or disruption of interactions between connexins and the Drebrin-containing submembrane cytoskeleton directs connexins to degradative cellular pathways [3].
• It is thus possible that Drebrin may interact with gap junctions in zones of cell-cell contacts in a regulated fashion in response to extracellular signals [3].
• CONCLUSIONS: We conclude that Drebrin is required for maintaining Cx43-containing gap junctions in their functional state at the plasma membrane [3].
• The novel Drebrin-Cx43 interaction identified by proteomics was confirmed by colocalization of endogenous proteins in astrocytes and Vero cells, coimmunoprecipitation, electron microscopy, electrophysiology, coexpression of both proteins with fluorescent tags, and live-cell FRET analysis [3].

Biological context of Dbn1

• Isoform specific expression of the neuronal F-actin binding protein, drebrin, in specialized cells of stomach and kidney epithelia [1].
• Our results confirm the role of drebrin E2 in the formation of branching processes and further indicate that during cell migration, the protein contributes to retraction of the cell body and the tail but not to lamellipodia formation [4].
• These findings suggest that s-drebrin A has a role in spine morphogenesis, possibly by competing the actin-binding activity with drebrin A [5].
• It contains a drebrin homology sequence in its N-terminal region and a cortactin homology sequence (SH3 domain) in its C-terminal region [6].
• Neurite-like processes in fibroblasts may be formed due to changes in microfilaments resulting from transfection of the drebrin (actin-binding protein) gene [2].

Anatomical context of Dbn1

• Using nanoelectrospray mass spectrometry methods, we initially identified drebrin in non-neuronal cultured cells [1].
• Recent studies have also detected the isoform drebrin E2 in a wide range of non-neuronal cell types, notably in and near actin-rich lamellipodia and filopodia [7].
• Drebrin was expressed as well in the distal tubule epithelial cells where the protein was concentrated at the luminal surface and present at the interdigitations of the basolateral membranes [1].
• Drebrin A, a major neuronal actin-binding protein, regulates the dendritic spine shapes of neurons [5].
• Immunohistochemistry using MAb G650 demonstrated that this myosin IIB-like immunreactivity can be detected in the neuronal cell bodies and their apical dendrites, where drebrin is hardly detected [8].

Physical interactions of Dbn1

• Immunoblotting with this antibody revealed that drebrin-binding cytoskeleton contains this myosin IIB-like immunreactivity [8].
• In cultured granule cells 7 days in vitro, Cupidin was present as synaptic and extra-synaptic punctate clusters that largely co-localized with the actin-cytoskeletal binding partners F-actin and drebrin, as well as a post-synaptic scaffold protein PSD-95 [9].

Regulatory relationships of Dbn1

• Stability of the distribution of spines containing drebrin A in the sensory cortex layer I of mice expressing mutated APP and PS1 genes [10].

Other interactions of Dbn1

• Non-muscle myosin IIB-like immunoreactivity is present at the drebrin-binding cytoskeleton in neurons [8].
• Thus, soluble Abeta could affect spines lacking drebrin A more strongly than spines containing drebrin A [10].
• The amino acid (aa) sequence of rat V-1, a developmentally regulated brain protein, was used to isolate clones encoding mouse V-1, a protein of 118 aa, from an embryoid body cDNA library [11].
• Expression of calmin, a novel developmentally regulated brain protein with calponin-homology domains [12].
• Expression of total CaMKII, total and pMAPK, total and pcreb, trk B and drebrin was comparable between groups [13].

Analytical, diagnostic and therapeutic context of Dbn1

• Drebrin protein detected in the non-brain organs migrated faster through SDS-PAGE gels, indicating that the lower molecular weight embryonic brain isoform (E2) may be the prominent isoform in these organs [1].
• Double-label immunofluorescence experiments of cultured cell monolayers revealed the localization of drebrin at the apical plasma membrane together with a pool of submembranous F-actin [1].
• Rapid isolation of tissue-specific and developmentally regulated brain cDNAs using RNA arbitrarily primed PCR (RAP-PCR) [14].

References