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Human zonulin, a potential modulator of intestinal tight junctions
W Wang1, S Uzzau, S E Goldblum
1Division of Pediatric Gastroenterology and Nutrition, Gastrointestinal Pathophysiology Section, Center for Vaccine Development, Baltimore, MD 21201, USA.
Journal of Cell Science
|November 18, 2000
Summary
Researchers discovered zonulin, a protein that mimics cholera toxin
Area of Science:
- Gastroenterology
- Molecular Biology
- Cell Biology
Background:
- Intercellular tight junctions regulate intestinal epithelial transport.
- Cholera's zonula occludens toxin modulates tight junction permeability.
- An endogenous modulator of tight junctions was hypothesized.
Purpose of the Study:
- To identify mammalian analogues of zonula occludens toxin.
- To investigate the role of these analogues in intestinal tight junction regulation.
Main Methods:
- Screening of fetal and adult human intestine using anti-zonula occludens toxin antibodies.
- Ussing chamber assay to assess tight junction permeability.
- Amino acid comparison between toxin and identified protein.
Main Results:
- A novel protein, zonulin, was identified in human intestine.
- Zonulin induces tight junction disassembly in primate intestinal epithelia.
- A putative receptor binding domain was identified in the N-terminal region.
Conclusions:
- Zonulin is an endogenous modulator of intestinal tight junctions.
- Zonulin plays a role in development, physiology, and disease.
- It influences fluid, macromolecule, and leukocyte movement and inflammatory disorders.