CLMP, a novel member of the CTX family and a new component of epithelial tight junctions

• The CTX family is a growing group of type I transmembrane proteins within the immunoglobulin superfamily (IgSF). They localize to junctional complexes between endothelial and epithelial cells and seem to participate in cell-cell adhesion and transmigration of leukocytes. Here, we report the identification of a new member of the CTX family. This protein, which was designated CLMP (coxsackie- and adenovirus receptor-like membrane protein), is composed of 373 amino acids including an extracellular part containing a V- and a C2-type domain, a transmembrane region and a cytoplasmic tail. CLMP mRNA was detected in a variety of both human and mouse tissues and cell lines. The protein migrated with an Mr of around 48 on SDS-PAGE and was predominantly expressed in epithelial cells within different tissues. In cultured epithelial cells, CLMP was detected in areas of cell-cell contacts. When exogenously expressed in polarized MDCK cells, CLMP was restricted to the subapical area of the lateral cell surface, where it co-localized with the tight junction markers ZO-1 and occludin. Also endogenous CLMP showed association with tight junctions, as analyzed in polarized human CACO-2 cells. This suggested a role for CLMP in cell-cell adhesion and indeed, overexpressed CLMP induced aggregation of non-polarized CHO cells. Furthermore, CLMP-expressing MDCK cells showed significantly increased transepithelial resistance, indicating a role for CLMP in junctional barrier function. Thus, we conclude that CLMP is a novel cell-cell adhesion molecule and a new component of epithelial tight junctions. We also suggest, based on phylogenetic studies, that CLMP, CAR, ESAM, and BT-IgSF form a new group of proteins within the CTX family.

Nyckelord

Amino Acid Sequence

Animals

Base Sequence

Cell Adhesion Molecules/chemistry/genetics/physiology

Cloning; Molecular

Colonic Neoplasms

Conserved Sequence

DNA Primers

Databases; Nucleic Acid

Epithelial Cells/*physiology

Humans

Membrane Proteins/chemistry/genetics/*physiology

Mice

Molecular Sequence Data

Phylogeny

Recombinant Proteins/chemistry

Sequence Alignment

Sequence Homology; Amino Acid

Tight Junctions/*physiology

Tumor Cells; Cultured

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