Nectin-3, a new member of immunoglobulin-like cell adhesion molecules that shows homophilic and heterophilic cell-cell adhesion activities.
We have isolated a novel cell-cell adhesion system localized at cadherin-based adherens junctions (AJs). This system consists of at least nectin, a Ca(2+)-independent immunoglobulin-like adhesion molecule, and afadin, an actin filament-binding protein, that connects nectin to the actin cytoskeleton. Nectin constitutes a family consisting of two members, nectin-1 and -2. ... We have isolated here a third member of the nectin family and named it nectin-3. Nectin-3 has three splicing variants, nectin-3alpha (biggest), -3beta (middle), and -3gamma (smallest). Like nectin-1 and -2, nectin-3alpha consists of three extracellular immunoglobulin-like domains, a transmembrane segment, and a cytoplasmic region with the C-terminal consensus motif for binding to the PDZ domain. Nectin-3alpha formed a cis-homo-dimer and showed Ca(2+)-independent trans-homo-interaction to cause homophilic cell-cell adhesion. Nectin-3alpha furthermore showed trans-hetero-interaction with nectin-1 or -2 but did not form a cis-hetero-dimer with nectin-1 or -2. Nectin-1 did not show trans-hetero-interaction with nectin-2. The affinity of trans-hetero-interaction of nectin-3alpha with nectin-1 or -2 was higher than that of trans-homo-interaction of nectin-1, -2, or -3alpha. Nectin-2 and -3 were ubiquitously expressed, whereas nectin-1 was abundantly expressed in brain. Nectin-3alpha was colocalized with nectin-2 at cadherin-based AJs and interacted with afadin. These results indicate that the nectin family consists of at least three members, nectin-1, -2, and -3, all of which show homophilic and heterophilic cell-cell adhesion activities and are localized at cadherin-based AJs.
Mesh Terms:
Alternative Splicing, Amino Acid Sequence, Animals, Brain, COS Cells, Cell Adhesion, Cell Adhesion Molecules, Cell Aggregation, Cross-Linking Reagents, Expressed Sequence Tags, Genetic Variation, Kidney, L Cells (Cell Line), Liver, Male, Mice, Molecular Sequence Data, Myocardium, Protein Isoforms, Recombinant Proteins, Sequence Alignment, Sequence Homology, Amino Acid, Spleen, Testis, Transfection
Alternative Splicing, Amino Acid Sequence, Animals, Brain, COS Cells, Cell Adhesion, Cell Adhesion Molecules, Cell Aggregation, Cross-Linking Reagents, Expressed Sequence Tags, Genetic Variation, Kidney, L Cells (Cell Line), Liver, Male, Mice, Molecular Sequence Data, Myocardium, Protein Isoforms, Recombinant Proteins, Sequence Alignment, Sequence Homology, Amino Acid, Spleen, Testis, Transfection
J. Biol. Chem.
Date: Apr. 07, 2000
PubMed ID: 10744716
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