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Troyanovsky, R. B.

Publications and source records attributed to Troyanovsky, R. B..

2 recordsLinked to original sources

Two δ-Catenins, Plakophilin 4 and p120, Promote Formation of Distinct Types of Adherens Junctions

Classic cadherins are instrumental for joining cells into tissues by producing cell-cell adhesions known as adherens junctions (AJs). These morphologically diverse structures are tailored to the specific cell sites, type of cells, and particular functions. The mechanism of AJ diversification remains unknown. Here we show that two members of the {delta}-catenin protein family, p120 and plakophilin 4 (pkp4), which interact with the juxtamembrane intracellular region of classic cadherins, promote distinct types of cadherin clustering thereby contributing to AJ specialization. The type controlled by p120 is driven by interactions between cadherin-associated protein, -catenin, and actin filaments. This "canonical" clustering mechanism results in formation of AJs that play a major role in overall cell-cell adhesion. The type promoted by pkp4 is driven by an -catenin-independent cadherin-F-actin interaction. It generates the so-called lateral spot AJs, which apparently function in processes other than cell-cell adhesion. Collectively, our study shows how {delta}-catenins regulate a balance between different types of AJs in epithelial cells.

cell biology↗

Characterization of early and late events of adherens junction assembly

Cadherins are transmembrane adhesion receptors. Cadherin ectodomains form adhesive 2D clusters through cooperative trans and cis interactions, whereas its intracellular region interacts with specific cytosolic proteins, termed catenins, to anchor the cadherin-catenin complex (CCC) to the actin cytoskeleton. How these two types of interactions are coordinated in the formation of specialized cell-cell adhesions, adherens junctions (AJ), remains unclear. We focus here on the role of the actin-binding domain of -catenin (ABD) by showing that the interaction of ABD with actin generates actin-bound CCC oligomers (CCC/actin strands) incorporating up to six CCCs. The strands are primarily formed on the actin-rich cell protrusions. Once in cell-cell interface, the strands become involved in cadherin ectodomain clustering. Such combination of the extracellular and intracellular oligomerizations gives rise to the composite oligomers, trans CCC/actin clusters. To mature, these clusters then rearrange their actin filaments using several redundant pathways, two of which are characterized here: one depends on the -catenin-associated protein, vinculin and the second one depends on the unstructured C-terminus of ABD. Thus, AJ assembly proceeds through spontaneous formation of trans CCC/actin clusters and their successive reorganization.

cell biology↗