Classic cadherins are transmembrane adhesive receptors that form adhesive contacts between cells in solid tissue. On the extracellular side of the plasma membrane, cadherins interact with one another, forming complexes that establish direct contacts between opposing cells. The intracellular cadherin portion is integrated in the cytoplasmic plaque, serving as anchorage sites for actin microfilaments. It is widely accepted that this type of adhesion, which is cell type-specific, provides a key driving force in the development of highly-ordered tissue architecture. Malfunctions in cadherin-based adhesion, which often accompany malignant transformation, contribute to high invasiveness of tumor cells.
Little has been known about how cadherin molecules interact with each other to establish the adhesive link. To shed light upon this question, we studied intercadherin interactions in epithelial cells. Our experiments reveal a critical cadherin-cadherin interaction resulting in the formation of adhesive cadherin dimers. We present strong evidence that the continuous formation of these short-lived adhesive dimers is a basic mechanism of cadherin-mediated adhesion. Assembly-disassembly cycle of such dimers is regulated by intracellular proteins including ß-catenin. The cellular systems regulating the lifetime of the adhesive dimers are a central subject of our current research.
Publications:
Troyanovsky RB, Sokolov E, Troyanovsky SM. Endocytosi of cadherin from intracellular junctions is the driving force for cadherin adhesive dimer disassembly. Mol Biol Cell 2006 17:3484-3493.
Troyanovsky SM. Cadherin dimers in cell-cell adhesion. Eur J Cell Biol 2005 84:225-233.
Klingelhöfer J, Troyanovsky RB, Laur OY, Troyanovsky SM. Exchange of catenins in cadherin-catenin complex. Oncogene 2003 22:1181-1188.
Troyanovsky RB, Sokolov E, Troyanovsky SM. Adhesive and lateral E-cadherin dimers are mediated by the same interface. Mol Cell Biol 2003 23:7965-7972.
Klingelhofer J, Laur OY, Troyanovsky RB, Troyanovsky SM. Dynamic interplay between adhesive and lateral E-cadherin dimers. Mol Cell Biol 2002 22:7449-7458.
