Journal Article

Involvement of nectin in the localization of junctional adhesion molecule at tight junctions

Shimizu, Kazuya, Kawakatsu, Tomomi, Kita, Toru, Nakanishi, Hiroyuki, Irie, Kenji, Sato, Tatsuhiro, Katata, Tatsuo, Takekuni, Kyoji, Horiuchi, Hisanori, Fukuhara, Atsunori, Takai, Yoshimi, Yamada, Akio, Ikeda, Wataru, Honda, Tomoyuki, Ozaki, Harunobu

2002

Overview

Junctional adhesion molecule (JAM) is a Ca2+-independent immunoglobulin-like cell-cell adhesion molecule which localizes at tight junctions (TJs). Claudin is a key cell-cell adhesion molecule that forms TJ strands at TJs. JAM is associated with claudin through their cytoplasmic tail-binding protein, ZO-1. JAM is furthermore associated with Par-3, a cell polarity protein which forms a ternary complex with Par-6 and atypical protein kinase C. Nectin is another Ca2+-independent immunoglobulin-like cell-cell adhesion molecule which localizes at adherens junctions (AJs). Nectin is associated with E-cadherin through their respective cytoplasmic tail-binding proteins, afadin and catenins, and involved in the formation of AJs cooperatively with E-cadherin. We show here that nectin is furthermore involved in the localization of JAM at TJs. During the formation of the junctional complex consisting of AJs and TJs in Madin-Darby canine kidney (MDCK) cells, JAM was recruited to the nectin-based cell-cell adhesion sites. This recruitment of JAM was inhibited by nectin inhibitors, which inhibited the trans-interaction of nectin. Microbeads coated with the extracellular fragment of nectin, that interacted with cellular nectin, also recruited JAM to the bead-MDCK cell contact sites. Furthermore, when cadherin-deficient L fibroblasts stably expressing both exogenous JAM and nectin (nectin-JAM-L cells) were co-cultured with L fibroblasts expressing only nectin (nectin-L cells), JAM was concentrated at the cell-cell adhesion sites between nectin-JAM-L and nectin-L cells without the trans-interaction of JAM. Analyses of the localization and immunoprecipitation of JAM revealed that it was associated with nectin through afadin and ZO-1. These results suggest that nectin has a role in the localization of JAM at TJs in the process of the formation of the junctional complex in epithelial cells.

• Publisher: Nature Publishing,Nature Publishing Group
• Subject: Adherens junctions / Animals / Biological and medical sciences / Cadherins - genetics / Cadherins - metabolism / Calcium - metabolism / Cell adhesion & migration / Cell Adhesion - drug effects / Cell Adhesion - physiology / Cell adhesion molecules / Cell Adhesion Molecules - drug effects / Cell Adhesion Molecules - genetics / Cell Adhesion Molecules - metabolism / Cell physiology / Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes / Cells, Cultured / Coculture Techniques / Dogs / E-cadherin / Epithelial cells / Epithelial Cells - drug effects / Epithelial Cells - metabolism / Fibroblasts / Fibroblasts - drug effects / Fundamental and applied biological sciences. Psychology / Genetic aspects / Health aspects / Immunoglobulins / Immunoprecipitation / Intercellular Junctions - metabolism / Junctional Adhesion Molecules / Kidney - cytology / Kinases / L cells / Localization / Medicine / Membrane Proteins - genetics / Membrane Proteins - metabolism / Microfilament Proteins - genetics / Microfilament Proteins - metabolism / Microspheres / Molecular and cellular biology / Molecular genetics / Mutagenesis. Repair / Nectin / Nectins / Phosphoproteins - genetics / Phosphoproteins - metabolism / Physiological aspects / Polarity / Protein kinase C / Proteins / Recombinant Proteins - genetics / Recombinant Proteins - metabolism / Structure / Tetradecanoylphorbol Acetate - pharmacology / Tight junctions / Tumor proteins / Zonula Occludens-1 Protein