Interaction of Nectin with Afadin Is Necessary for Its Clustering at Cell-Cell Contact Sites but Not for Itscis Dimerization or trans Interaction

• Published in: The Journal of biological chemistry Vol. 275; no. 1; pp. 613 - 618
• Main Authors: Miyahara, Masako, Nakanishi, Hiroyuki, Takahashi, Kenichi, Satoh-Horikawa, Keiko, Tachibana, Kouichi, Takai, Yoshimi
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 07.01.2000
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.275.1.613

We have recently found a novel functional unit of cell-cell adhesion at cadherin-based adherens junctions, consisting of at least nectin, a homophilic cell adhesion molecule, and afadin, an actin filament-binding protein, which connects nectin to the actin cytoskeleton. Here we studied a mechanism of cell-cell adhesion of the nectin-afadin system by use of a cadherin-deficient L cell line stably expressing the intact form of mouse nectin-2α, a truncated form of nectin-2α incapable of interacting with afadin (nectin-2α-ΔC), or a point-mutated form of nectin-2α capable of interacting with afadin and a cadherin-expressing EL cell line, which transiently expressed the point-mutated form of nectin-2α. We found that the interaction of nectin-2α with afadin was necessary for their clustering at cell-cell contact sites. However, nectin-2α-ΔC showed cis dimerization and trans interaction, both of which did not require the interaction of nectin-2α with afadin. We have previously shown in EL cells that the interaction of nectin-1 with afadin is necessary for its recruitment to adherens junctions. We found that the trans interaction of nectin-2α was furthermore necessary for this recruitment. On the basis of these observations, we propose a model for the mechanism of cell-cell adhesion of nectin and roles of afadin in this mechanism.