A comparative molecular force spectroscopy study of homophilic JAM-A interactions and JAM-A interactions with reovirus attachment protein σ1

✍ Scribed by Sri Ram Krishna Vedula; Tong Seng Lim; Eva Kirchner; Kristen M. Guglielmi; Terence S. Dermody; Thilo Stehle; Walter Hunziker; Chwee Teck Lim

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 309 KB
• Volume: 21
• Category: Article
• ISSN: 0952-3499
• DOI: 10.1002/jmr.886

✦ Synopsis

Abstract

JAM‐A belongs to a family of immunoglobulin‐like proteins called junctional adhesion molecules (JAMs) that localize at epithelial and endothelial intercellular tight junctions. JAM‐A is also expressed on dendritic cells, neutrophils, and platelets. Homophilic JAM‐A interactions play an important role in regulating paracellular permeability and leukocyte transmigration across epithelial monolayers and endothelial cell junctions, respectively. In addition, JAM‐A is a receptor for the reovirus attachment protein, σ1. In this study, we used single molecular force spectroscopy to compare the kinetics of JAM‐A interactions with itself and σ1. A chimeric murine JAM‐A/Fc fusion protein and the purified σ1 head domain were used to probe murine L929 cells, which express JAM‐A and are susceptible to reovirus infection. The bond half‐life (t~1/2~) of homophilic JAM‐A interactions was found to be shorter ($k_{{\bf off}}^{\bf o} = 0.688 \pm 0.349;{\bf s}^{ - 1} $) than that of σ1/JAM‐A interactions ($k_{{\bf off}}^{\bf o} = 0.067 \pm 0.041;{\bf s}^{ - 1} $). These results are in accordance with the physiological functions of JAM‐A and σ1. A short bond lifetime imparts a highly dynamic nature to homophilic JAM‐A interactions for regulating tight junction permeability while stable interactions between σ1 and JAM‐A likely anchor the virus to the cell surface and facilitate viral entry. Copyright © 2008 John Wiley & Sons, Ltd.