Biomedical subjects

Oscar Y Laur

Publications and source records attributed to Oscar Y Laur.

3 recordsLinked to original sources

PubMed2003

Exchange of catenins in cadherin-catenin complex.

beta-Catenin is an intracellular multifunctional protein. In complex with the transmembrane adhesive receptor E-cadherin, it becomes plasma membrane-associated and mediates intercellular adhesion. A cytosolic pool of beta-catenin interacts with DNA-binding proteins and participates in signal transduction. To reveal the possible cross-talk between these two pools, we studied whether beta-catenin is exchanged between its free and cadherin-bound states. We found that pulse-labeled beta-catenin replaces the beta-catenin bound to the cell surface prebiotinylated E-cadherin immediately after synthesis. Approximately 25% of all pulse-labeled beta-catenin destined for E-cadherin associates with this protein via this mechanism. The rest of the newly synthesized beta-catenin arrives at the plasma membrane in a complex with the E-cadherin precursor. Immediately after arrival, this beta-catenin pool is transferred to the prebiotinylated E-cadherin. beta-Catenin released from E-cadherin may participate in new exchange cycles. This beta-catenin exchange is strongly affected in cells that contain mutations in the tumor suppressor gene APC. This process may contribute significantly to both cell-cell adhesion and beta-catenin-dependent signaling.

Adenocarcinoma↗

PubMed2002

Both the dimerization and immunochemical properties of E-cadherin EC1 domain depend on Trp(156) residue.

Using site-directed mutagenesis, we show in this paper that the adhesive interface detected in cadherin crystals is unlikely to mediate adhesive interaction between myc- and flag-tagged E-cadherin molecules in human A-431 cells. We also found that a critical residue within this interface, His(233), is part of the epitope for mAb SHE78-7. This epitope was accessible to the antibody in the adhesive E-cadherin dimers, which is consistent with uninvolvement of the site containing His(233) in cell-cell adhesion. However, both the adhesive dimerization and the integrity of the SHE78-7 epitope depended on the same intramolecular interaction between Trp(156) and its hydrophobic pocket. Our data suggest that this interaction may have an important regulatory function in controlling the surface topology of the NH(2)-terminal domain of E-cadherin.

Amino Acid Sequence↗

PubMed2002

Dynamic interplay between adhesive and lateral E-cadherin dimers.

E-cadherin, an adhesive transmembrane protein of epithelial adherens junctions, forms two types of detergent-resistant dimers: adhesive dimers consisting of cadherin molecules derived from two neighboring cells and lateral dimers incorporating cadherins of the same cell. Both dimers depend on the integrity of the same residue, Trp156. While the relative amounts of these complexes are not certain, we show here that in epithelial A-431 cells, adhesive dimers may be a prevalent form. Inactivation of the calcium-binding sites, located between successive cadherin ectodomains, drastically reduced the amount of adhesive dimers and concomitantly increased the amount of lateral dimers. A similar interdependence of adhesive and lateral dimers was observed in digitonin-permeabilized cells. In these cells, adhesive dimers immediately disassembled after lowering the Ca2+ concentration below 0.1 mM. The disappearance of adhesive dimers was counterbalanced by an increase in Trp156-dependent lateral dimers. Increasing the calcium concentration to a normal level rapidly restored the original balance between adhesive and lateral dimers. We also present evidence that E-cadherin dimers in vivo have a short lifetime. These observations suggest that cadherin-mediated adhesion is based on the dynamic cycling of E-cadherin between monomeric and adhesive dimer states.

Binding Sites↗