Nectin/PRR: An Immunoglobulin-like Cell Adhesion Molecule Recruited to Cadherin-based Adherens Junctions through Interaction with Afadin, a PDZ Domain–containing Protein

Abstract

We have isolated a novel actin filament–binding protein, named afadin, localized at cadherin-based cell–cell adherens junctions (AJs) in various tissues and cell lines. Afadin has one PDZ domain, three proline-rich regions, and one actin filament–binding domain. We found here that afadin directly interacted with a family of the immunoglobulin superfamily, which was isolated originally as the poliovirus receptor–related protein (PRR) family consisting of PRR1 and -2, and has been identified recently to be the alphaherpes virus receptor. PRR has a COOH-terminal consensus motif to which the PDZ domain of afadin binds. PRR and afadin were colocalized at cadherin-based cell–cell AJs in various tissues and cell lines. In E-cadherin–expressing EL cells, PRR was recruited to cadherin-based cell–cell AJs through interaction with afadin. PRR showed Ca2+-independent cell–cell adhesion activity. These results indicate that PRR is a cell–cell adhesion molecule of the immunoglobulin superfamily which is recruited to cadherin-based cell–cell AJs through interaction with afadin. We rename PRR as nectin (taken from the Latin word “necto” meaning “to connect”).

Rap1: a key regulator in cell-cell junction formation

“…One protein heavily involved in this process is afadin/AF6, an adaptor protein that binds to various junctional proteins, such as nectins, ZO-1 and JAM-A (Boettner et al, 2000;Ebnet et al, 2000;Takahashi et al, 1999). Afadin/AF6 has two Ras-association (RA) domains, which can bind to both Ras and Rap1.…”

Adherens Junction: Molecular Architecture and Regulation

“…Afadin, on the other hand, was shown to interact with a-catenin, suggesting that a physical association might occur between the cadherin -catenin and nectin -afadin complexes (Tachibana et al 2000). Because afadin is an actin-binding protein (Mandai et al 1997;Takahashi et al 1999), this system may also play a role in the linking of AJ to actin filaments.…”

Similar and differential behaviour between the nectin‐afadin‐ponsin and cadherin‐catenin systems during the formation and disruption of the polarized junctional alignment in epithelial cells

“…Ponsin has at least 12 splicing variants, one of which is identical to SH3P12/CAP (Sparks et al 1996;Ribon et al 1998). The NAP system is colocalized with the cadherin-catenin system at cell-cell AJs, and it is more highly concentrated there than the cadherin-catenin system in polarized epithelial cells (Mandai et al 1997(Mandai et al , 1999Takahashi et al 1999). In this study, we examined the behaviour of the NAP system in comparison with that of the cadherin-catenin system during the formation and disruption of the polarized junctional alignment in epithelial cells.…”