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PMID:16188940

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Citation

Osler, ME, Chang, MS and Bader, DM (2005) Bves modulates epithelial integrity through an interaction at the tight junction. J. Cell. Sci. 118:4667-78

Abstract

We first identified Bves (blood vessel/epicardial substance) as a transmembrane protein that localized to the lateral compartment of the epithelial epicardium. Bves traffics to sites of cell-cell contact in cultured epicardial cells and promotes adhesion following transfection into non-adherent fibroblastic L-cells, reminiscent of a cell adhesion molecule. Currently, no function for Bves in relation to epithelial cell adhesion has been identified. We hypothesize that Bves plays a role at cell junctions to establish and/or modulate cell adhesion or cell-cell interactions in epithelial cell types. In this study, we demonstrate that Bves regulates epithelial integrity and that this function may be associated with a role at the tight junction (TJ). We report that Bves localizes with ZO-1 and occludin, markers of the TJ, in polarized epithelial cell lines and in vivo. We find that the behavior of Bves following low Ca2+ challenge or TPA treatment mimics that observed for ZO-1 and is distinct from adherens junction proteins such as E-cadherin. Furthermore, GST pull-down experiments show an interaction between ZO-1 and the intracellular C-terminal tail of Bves. Finally, we demonstrate that Bves modulates tight junction integrity, as indicated by the loss of transepithelial resistance and junction protein localization at the membrane following Bves knock-down in cultured cells. This study is the first to identify a function for Bves in epithelia and supports the hypothesis that Bves contributes to establishment and/or maintenance of epithelial cell integrity.

Links

PubMed Online version:10.1242/jcs.02588

Keywords

Animals; Avian Proteins/chemistry; Avian Proteins/deficiency; Avian Proteins/genetics; Avian Proteins/metabolism; Biological Transport; Cadherins/metabolism; Calcium/pharmacology; Cell Adhesion/drug effects; Cell Adhesion Molecules/chemistry; Cell Adhesion Molecules/deficiency; Cell Adhesion Molecules/genetics; Cell Adhesion Molecules/metabolism; Cell Line; Cell Membrane/metabolism; Chickens; Dogs; Epithelial Cells/cytology; Epithelial Cells/metabolism; Epithelial Cells/ultrastructure; Golgi Apparatus; Humans; Membrane Proteins/metabolism; Muscle Proteins/chemistry; Muscle Proteins/deficiency; Muscle Proteins/genetics; Muscle Proteins/metabolism; Mutagenesis; Phorbol Esters/pharmacology; Phosphoproteins/metabolism; Protein Binding; Tight Junctions/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:ZO1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9ES83

F

Seeded From UniProt

complete

HUMAN:POPD1

enables

GO:0005198: structural molecule activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:POPD1

located_in

GO:0016328: lateral plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:POPD1

located_in

GO:0005923: bicellular tight junction

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:POPD1

located_in

GO:0016021: integral component of membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:POPD1

involved_in

GO:0090136: epithelial cell-cell adhesion

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:POPD1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P39447

F

Seeded From UniProt

complete

MOUSE:POPD1

located_in

GO:0016328: lateral plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:POPD1

located_in

GO:0005923: bicellular tight junction

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:POPD1

located_in

GO:0016021: integral component of membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CHICK:POPD1

enables

GO:0005198: structural molecule activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CHICK:POPD1

involved_in

GO:0090136: epithelial cell-cell adhesion

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:Q9DG21

enables

GO:0005198: structural molecule activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CHICK:Q9DG21

involved_in

GO:0090136: epithelial cell-cell adhesion

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:Q9DG22

enables

GO:0005198: structural molecule activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CHICK:Q9DG22

involved_in

GO:0090136: epithelial cell-cell adhesion

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:Q9DG23

enables

GO:0005198: structural molecule activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CHICK:Q9DG23

involved_in

GO:0090136: epithelial cell-cell adhesion

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:Q9PWC0

enables

GO:0005198: structural molecule activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CHICK:Q9PWC0

involved_in

GO:0090136: epithelial cell-cell adhesion

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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