Gene expression of the tight junction protein occludin includes differential splicing and alternative promoter usage

Occludin is an integral membrane protein located at the tight junctions of epithelial cells. Multiple domains of occludin are involved in the regulation of paracellular permeability as well as in the targeting of the protein to the tight junction. In this study, different occludin variants were iden...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2002-11, Vol.298 (5), p.657-666
Main Authors: Mankertz, Joachim, Stefan Waller, Jörg, Hillenbrand, Bernd, Tavalali, Shida, Florian, Peter, Schöneberg, Torsten, Fromm, Michael, Dieter Schulzke, Jörg
Format: Article
Language:English
Subjects:
Alternative Splicing
Amino Acid Sequence
Base Sequence
Cell Line
DNA, Complementary - genetics
Exons
Gene Expression
Gene regulation
Genes, Reporter
Green Fluorescent Proteins
Humans
Introns
Luminescent Proteins - genetics
Luminescent Proteins - metabolism
Membrane Proteins - chemistry
Membrane Proteins - genetics
Membrane Proteins - metabolism
Molecular Sequence Data
Occludin
Promoter Regions, Genetic
Protein Structure, Tertiary
Recombinant Fusion Proteins - chemistry
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
Sequence Homology, Amino Acid
Subcellular Fractions - metabolism
Tight junction
Tight Junctions - genetics
Tight Junctions - metabolism
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Summary:Occludin is an integral membrane protein located at the tight junctions of epithelial cells. Multiple domains of occludin are involved in the regulation of paracellular permeability as well as in the targeting of the protein to the tight junction. In this study, different occludin variants were identified on the mRNA level. Four differentially spliced occludin-specific mRNA transcripts were detected. Expression of the resulting proteins revealed an altered subcellular distribution and a loss of co-localization with zonula occludens protein ZO-1 in the tight junction for two of the four splice variants. Our findings demonstrate that the fourth transmembrane domain of occludin is important for targeting occludin to the tight junction. Loss of the fourth transmembrane domain leads to a relocation of the C-terminal domain to the extracellular space. The structural diversity of natural occludin variants is further increased by an additional promoter and transcription start giving rise to an alternative exon 1. Gene expression mediated by this promoter is influenced by the pro-inflammatory cytokine tumor necrosis factor α.
ISSN:0006-291X
1090-2104
DOI:10.1016/S0006-291X(02)02487-7