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© The Rockefeller University Press, 0021-9525/2002/2/555 $5.00
The Journal of Cell Biology, Volume 156, Number 3, February 4, 2002 555-565

Nectin

Akira Mizoguchi^1,2, Hiroyuki Nakanishi³, Kazushi Kimura¹, Kaho Matsubara¹, Kumi Ozaki-Kuroda³, Tatsuo Katata³, Tomoyuki Honda³, Yoshimoto Kiyohara¹, Kyun Heo^1,2, Mikito Higashi², Tomonari Tsutsumi², Satomi Sonoda², Chizuka Ide¹ and Yoshimi Takai³

¹ Department of Anatomy and Neurobiology, Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan
² Department of Anatomy, Faculty of Medicine, Mie University, Tsu 514-8507, Japan
³ Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Japan

Address correspondence to Yoshimi Takai at the Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Osaka, Japan. Tel.: 81-66-879-3410. Fax: 81-66-879-3419. E-mail: ytakai{at}molbio.med.osaka-u.ac.jp

The nectin–afadin system is a novel cell–cell adhesion system that organizes adherens junctions cooperatively with the cadherin–catenin system in epithelial cells. Nectin is an immunoglobulin-like adhesion molecule, and afadin is an actin filament–binding protein that connects nectin to the actin cytoskeleton. Nectin has four isoforms (-1, -2, -3, and -4). Each nectin forms a homo-cis-dimer followed by formation of a homo-trans-dimer, but nectin-3 furthermore forms a hetero-trans-dimer with nectin-1 or -2, and the formation of each hetero-trans-dimer is stronger than that of each homo-trans-dimer. We show here that at the synapses between the mossy fiber terminals and dendrites of pyramidal cells in the CA3 area of adult mouse hippocampus, the nectin–afadin system colocalizes with the cadherin–catenin system, and nectin-1 and -3 asymmetrically localize at the pre- and postsynaptic sides of puncta adherentia junctions, respectively. During development, nectin-1 and -3 asymmetrically localize not only at puncta adherentia junctions but also at synaptic junctions. Inhibition of the nectin-based adhesion by an inhibitor of nectin-1 in cultured rat hippocampal neurons results in a decrease in synapse size and a concomitant increase in synapse number. These results indicate an important role of the nectin–afadin system in the formation of synapses.

Key Words: nectin; afadin; cadherin; puncta adherentia junctions; synaptic junctions

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