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").
MeSH terms
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Alternative Splicing / genetics
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Amino Acid Sequence
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Animals
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COS Cells / chemistry
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COS Cells / metabolism
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Cadherins / metabolism*
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Calcium / metabolism
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Cell Adhesion Molecules / chemistry
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Cell Adhesion Molecules / genetics*
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Cell Adhesion Molecules / metabolism
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Cell Aggregation / physiology
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Epithelial Cells / chemistry
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Epithelial Cells / cytology
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Epithelial Cells / metabolism
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Intercellular Junctions / chemistry
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Intercellular Junctions / metabolism*
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Intercellular Junctions / ultrastructure
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Kinesins
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Membrane Glycoproteins / chemistry
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism
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Mice
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Microfilament Proteins / chemistry
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Microfilament Proteins / metabolism*
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Microscopy, Electron
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Myocardium / chemistry
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Myocardium / cytology
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Myocardium / metabolism
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Myosins
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Nectins
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Protein Structure, Tertiary
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Rabbits
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Receptors, Tumor Necrosis Factor*
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Receptors, Tumor Necrosis Factor, Member 14
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Receptors, Virus*
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Vinculin / metabolism
Substances
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AFDN protein, human
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Afdn protein, mouse
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Cadherins
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Cell Adhesion Molecules
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Membrane Glycoproteins
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Microfilament Proteins
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Nectins
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Receptors, Tumor Necrosis Factor
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Receptors, Tumor Necrosis Factor, Member 14
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Receptors, Virus
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TNFRSF14 protein, human
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Tnfrsf14 protein, mouse
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afadin
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Vinculin
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Myosins
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Kinesins
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Calcium