Disease relevance of Dbnl

• By using Fyb domains as bait to screen a mouse lymphoma cDNA library, we identified a novel interaction partner, mammalian actin binding protein 1 (mAbp1) [1].
• Missing in metastasis (MIM) gene encodes an actin binding protein that is expressed at low levels in a subset of malignant cell lines [2].
• Since Nd1-L, a novel actin-binding protein, is expressed most abundantly in the heart of adult mice, we examined a role of Nd1-L in doxorubicin-induced cardiomyopathy [3].

Psychiatry related information on Dbnl

• Drebrin had previously been described as an actin binding protein that diminishes in brains during Alzheimer's disease [4].

High impact information on Dbnl

• By shadowing specimens dried onto mice sheets we have obtained clear images of actin crosslinked by spectrin, an actin-binding protein found in erythrocytes [5].
• These effects are mediated by two newly identified p53 transcriptional targets, the actin-binding protein Coronin 1b and the GTPase Rab13, both of which associate with the cytoskeleton and regulate neurite outgrowth [6].
• Structural properties, biochemical analysis of its interaction partners and siRNA studies implicated mAbp1 as an accessory protein in clathrin-mediated endocytosis (CME) [7].
• Here, we describe the generation and characterization of mice deficient for SH3P7/mAbp1 owing to targeted gene disruption in embryonic stem cells [7].
• SH3P7/mAbp1 deficiency leads to tissue and behavioral abnormalities and impaired vesicle transport [7].

Biological context of Dbnl

• Cortactin is an actin-binding protein that contains several potential signaling motifs including a Src homology 3 (SH3) domain at the distal C terminus [8].
• Among these, coronin 1A, an actin-binding protein, was identified as a molecule showing high expression in solid lymphoma by both DNA microarray and proteomics analyses [9].
• The actin-binding protein (ABP) drebrin, isoform E2, is involved in remodelling of the actin cytoskeleton and in formation of cell processes, but its role in cell migration has not yet been investigated [10].
• SH3P7 was originally isolated by cloning SH3 domain ligand targets from a mouse embryo cDNA library [11].
• Neurite-like processes in fibroblasts may be formed due to changes in microfilaments resulting from transfection of the drebrin (actin-binding protein) gene [12].

Anatomical context of Dbnl

• Growth factors cause mAbp1 to rapidly accumulate in lamellipodia [13].
• We found that the cytoplasmic adaptor HIP-55, a Src/Syk-kinases substrate and member of the drebrin/Abp1 family of actin-binding proteins, localized to the T cell-antigen-presenting cell (APC) contact site in an antigen-dependent manner [14].
• We have used fluorescent protein tagging to study the localization and dynamics of the actin-binding protein cortactin in living NIH 3T3 fibroblast cells [15].
• Double-labelling studies with anti-SH3P7 antibody and other neuronal marker proteins revealed that SH3P7 was located primarily in dendrites, and in moderate amounts in cell bodies [11].
• Cofilin is an actin-binding protein, which, when unphosphorylated, stimulates depolymerization and severing of actin filaments [16].

Associations of Dbnl with chemical compounds

• We have identified a gene encoding a mouse homologue of Abp1p, and it is identical to SH3P7, a protein shown recently to be a target of Src tyrosine kinases [13].
• We previously demonstrated that doxorubicin treatment of mice resulted in a selective decrease in expression of the Nd1 gene, which encoded a new kelch family actin binding protein in the heart [17].
• The inhibitory effect of a dynamin proline-rich domain deletion mutant on the recruitment of Abp1 to the plasma membrane, coimmunoprecipitation of dynamin with Abp1, and coprecipitation of Abp1 with GST fusion of the dyanmin proline-rich domain demonstrate the interaction of Abp1 with dynamin 2 [18].

Physical interactions of Dbnl

• We show that mAbp1 binds the Fyb N-terminal via its C-terminally located src homology 3 domain [1].

Other interactions of Dbnl

• Hence, mAbp1 is likely to constitute a downstream effector of Fyb involved in F-actin dynamics [1].
• Cttn encodes the actin-binding protein cortactin [19].

Analytical, diagnostic and therapeutic context of Dbnl

• Immunohistochemistry revealed that the most intense immunolabelling for SH3P7 was observed in the hippocampus and cerebellar cortex [11].
• Molecular cloning and dendritic localization of rat SH3P7 [11].
• Sequence analysis revealed that there were at least four isoforms of the SH3P7 protein: SH3P7r1-SH3P7r4 [11].
• Coronin, a 57 kDa actin binding protein elutes with an apparent molecular mass of 400-600 kDa from gel filtration columns [20].
• In the present study, we performed cDNA cloning of rat SH3P7, performed RT-PCR analysis, generated polyclonal antibodies against the recombinant rat SH3P7 protein, and examined the distribution of SH3P7 in the rat brain using immunohistochemistry [11].

References