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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Stevenson, B. R. Wittchen, E. S. Haskins, J. |
| Description | Author Affiliation: Wittchen ES ( Department of Cell Biology, University of Alberta, Edmonton, Alberta, Canada T6G 2H7.) |
| Abstract | The functional characteristics of the tight junction protein ZO-3 were explored through exogenous expression of mutant protein constructs in MDCK cells. Expression of the amino-terminal, PSD95/dlg/ZO-1 domain-containing half of the molecule (NZO-3) delayed the assembly of both tight and adherens junctions induced by calcium switch treatment or brief exposure to the actin-disrupting drug cytochalasin D. Junction formation was monitored by transepithelial resistance measurements and localization of junction-specific proteins by immunofluorescence. The tight junction components ZO-1, ZO-2, endogenous ZO-3, and occludin were mislocalized during the early stages of tight junction assembly. Similarly, the adherens junction proteins E-cadherin and β-catenin were also delayed in their recruitment to the cell membrane, and NZO-3 expression had striking effects on actin cytoskeleton dynamics. NZO-3 expression did not alter expression levels of ZO-1, ZO-2, endogenous ZO-3, occludin, or E-cadherin; however, the amount of Triton X-100–soluble, signaling-active β-catenin was increased in NZO-3–expressing cells during junction assembly. In vitro binding experiments showed that ZO-1 and actin preferentially bind to NZO-3, whereas both NZO-3 and the carboxy-terminal half of the molecule (CZO-3) contain binding sites for occludin and cingulin. We hypothesize that NZO-3 exerts its dominant-negative effects via a mechanism involving the actin cytoskeleton, ZO-1, and/or β-catenin. |
| ISSN | 00219525 |
| e-ISSN | 15408140 |
| Journal | The Journal of Cell Biology |
| Issue Number | 4 |
| Volume Number | 151 |
| Language | English |
| Publisher | Rockefeller University Press (United States) |
| Publisher Date | 2000-11-13 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Carrier Proteins Genetics Metabolism Membrane Proteins Tight Junctions Physiology Ultrastructure Trans-Activators Animals Cadherins Calcium Signaling Cell Line Cytoskeletal Proteins Epithelial Cells Cytology Gene Expression Regulation Occludin Peptide Fragments Biosynthesis Phosphoproteins Recombinant Proteins Transfection Zonula Occludens Proteins Zonula Occludens-1 Protein Zonula Occludens-2 Protein Beta Catenin Research Support, Non-U.S. Gov't Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine |
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