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Transmembrane proteins in the tight junction barrier.
A S Fanning1, L L Mitic, J M Anderson
1Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut 06520, USA.
Journal of the American Society of Nephrology : JASN
|June 11, 1999
Summary
Tight junctions regulate paracellular permeability via transmembrane proteins like occludin and claudins. These proteins, along with cytoplasmic scaffolding, control the passage of water, solutes, and immune cells.
Area of Science:
- Cell biology
- Molecular biology
- Physiology
Background:
- Tight junctions form a seal between epithelial and endothelial cells.
- The molecular mechanisms regulating paracellular permeability are not fully understood.
- Key transmembrane proteins at tight junctions include occludin, claudins, and junction adhesion molecules.
Purpose of the Study:
- To elucidate the molecular basis of paracellular permeability regulation by tight junction proteins.
- To understand how these proteins control the passage of water, solutes, and immune cells.
Main Methods:
- Identification and localization of transmembrane proteins within tight junctions.
- Analysis of the functional roles of occludin, claudins, and junction adhesion molecules.
- Investigation of the cytoplasmic protein plaque's scaffolding and signaling functions.
Main Results:
- Occludin influences ion and solute permeability.
- Claudins, a family of four-membrane spanning proteins, are integral to tight junctions.
- Junction adhesion molecule regulates immune cell transmigration.
- Cytoplasmic proteins link transmembrane proteins to the actin cytoskeleton for regulatory signaling.
Conclusions:
- Multiple transmembrane proteins within tight junctions, including occludin, claudins, and junction adhesion molecules, are critical for regulating paracellular transport.
- A cytoplasmic protein complex likely scaffolds these transmembrane proteins and transduces regulatory signals, controlling barrier function.
- Further research is needed to fully define the precise molecular interactions governing tight junction permeability.