PubMed Health⌕ Search

Biomedical subjects

Elena Korenbaum

Publications and source records attributed to Elena Korenbaum.

5 recordsLinked to original sources
PubMed2006

ErbB receptor dimerization, localization, and co-localization in mouse lung type II epithelial cells.

ErbB receptors are crucial for embryonic neuronal and cardiac development. ErbB receptor ligands neuregulin (NRG) and epidermal growth factor (EGF) play a major role in the developing lung, specifically in mesenchymal induced fetal surfactant synthesis by type II epithelial cells. Different erbB receptor ligands cause diverse biologic effects by stimulating specific erbB-dimers. It is not known how dimerization, cellular localization, and co-localization of erbB dimers are regulated in type II epithelial cells. We hypothesized that erbB receptors have a distinct dimerization, localization, and co-localization pattern in type II cells. In mouse type II epithelial cells, which express all four erbB receptors, erbB1 and erbB4 were the preferred dimerization partners. These dimerization patterns were ligand independent. Confocal microscopy showed these transmembrane receptors exhibited a strong nuclear localization. In non-stimulated cells, both erbB1 and erbB2 were predominantly localized to the nucleus and less intensely to the cytoplasm. However, erbB1 was mainly found in the nucleoli, whereas erbB2 spared the nucleolar region. ErbB3 was exclusively located in the nucleoli. ErbB4 was diffusely located in nucleus and cytoplasm, and like erbB2 spared the nucleolar region. Short stimulation with either EGF or NRG led to a more pronounced nuclear staining for erbB1, erbB2, and erbB4. All four receptors co-localized with each other after stimulation, but with varying intensity. The two known stimulators of fetal surfactant synthesis, NRG and NRG-containing fibroblast conditioned medium, changed cellular localization of the dimerization partners erbB4 and erbB2 in a distinct fashion. We conclude that erbB receptors have a receptor-specific localization and dimerization pattern in type II epithelial cells.

Animals↗
PubMed2004

Enaptin, a giant actin-binding protein, is an element of the nuclear membrane and the actin cytoskeleton.

Enaptin belongs to a family of recently identified giant proteins that associate with the F-actin cytoskeleton as well as the nuclear membrane. It is composed of an N-terminal alpha-actinin type actin-binding domain (ABD) followed by a long coiled coil rod and a transmembrane domain at the C-terminus. The ABD binds to F-actin in vivo and in vitro and leads to bundle formation. The human Enaptin gene spreads over 515 kb and gives rise to several splicing isoforms (Nesprin-1, Myne-1, Syne-1, CPG2). The longest assembled cDNA encompasses 27,669 bp and predicts a 1014 kDa protein. Antibodies against the ABD of Enaptin localise the protein at F-actin-rich structures throughout the cell and in focal contacts as well as at the nuclear envelope. In COS7 cells, the protein is also present within the nuclear compartment. With the discovery of the actin-binding properties of Enaptin and the highly homologous Nuance, we define a family of proteins that integrate the cytoskeleton with the nucleoskeleton.

Actinin↗
PubMed2002

NUANCE, a giant protein connecting the nucleus and actin cytoskeleton.

NUANCE (NUcleus and ActiN Connecting Element) was identified as a novel protein with an alpha-actinin-like actin-binding domain. A human 21.8 kb cDNA of NUANCE spreads over 373 kb on chromosome 14q22.1-q22.3. The cDNA sequence predicts a 796 kDa protein with an N-terminal actin-binding domain, a central coiled-coil rod domain and a predicted C-terminal transmembrane domain. High levels of NUANCE mRNA were detected in the kidney, liver, stomach, placenta, spleen, lymphatic nodes and peripheral blood lymphocytes. At the subcellular level NUANCE is present predominantly at the outer nuclear membrane and in the nucleoplasm. Domain analysis shows that the actin-binding domain binds to Factin in vitro and colocalizes with the actin cytoskeleton in vivo as a GFP-fusion protein. The C-terminal transmembrane domain is responsible for the targeting the nuclear envelope. Thus, NUANCE is the first alpha-actinin-related protein that has the potential to link the microfilament system with the nucleus.

Actin Cytoskeleton↗
PubMed2002

The role of MeH73 in actin polymerization and ATP hydrolysis.

In actin from many species H73 is methylated, but the function of this rare post-translational modification is unknown. Although not within bonding distance, it is located close to the gamma-phosphate of the actin-bound ATP. In most crystal structures of actin, the delta1-nitrogen of the methylated H73 forms a hydrogen bond with the carbonyl of G158. This hydrogen bond spans the gap separating subdomains 2 and 4, thereby contributing to the forces that close the interdomain cleft around the ATP polyphosphate tail. A second hydrogen bond stabilizing interdomain closure exists between R183 and Y69. In the closed-to-open transition in beta-actin, both of these hydrogen bonds are broken as the phosphate tail is exposed to solvent. Here we describe the isolation and characterization of a mutant beta-actin (H73A) expressed in the yeast Saccharomyces cerevisiae. The properties of the mutant are compared to those of wild-type beta-actin, also expressed in yeast. Yeast does not have the methyl transferase necessary to methylate recombinant beta-actin. Thus, the polymerization properties of yeast-expressed wild-type beta-actin can be compared with normally methylated beta-actin isolated from calf thymus. Since earlier studies of the actin ATPase almost invariably employed rabbit skeletal alpha-actin, this isoform was included in these comparative studies on the polymerization, ATP hydrolysis, and phosphate release of actin. It was found that H73A-actin exchanged ATP at an increased rate, and was less stable than yeast-expressed wild-type actin, indicating that the mutation affects the spatial relationship between the two domains of actin which embrace the nucleotide. At physiological concentrations of Mg(2+), the kinetics of ATP hydrolysis of the mutant actin were unaffected, but polymer formation was delayed. The comparison of methylated and unmethylated beta-actin revealed that in the absence of a methyl group on H73, ATP hydrolysis and phosphate release occurred prior to, and seemingly independently of, filament formation. The comparison of beta and alpha-actin revealed differences in the timing and relative rates of ATP hydrolysis and P(i)-release.

Actins↗