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

TLDR

Afadin contains a PDZ domain, proline‑rich regions, and an actin‑binding domain, while PRR possesses a C‑terminal motif that binds afadin’s PDZ domain. The study proposes renaming the poliovirus receptor‑related protein (PRR) as nectin to reflect its adhesive function. The authors identified afadin as an actin‑filament binding protein localized at cadherin‑based adherens junctions, demonstrated that it directly binds the PRR family (now called nectin) through its PDZ domain, and showed that nectin is recruited to these junctions and mediates Ca²⁺‑independent cell‑cell adhesion.

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").