29.11
Tight Junctions
In organs such as kidneys and intestines, the epithelial cells are sealed together with tight junctions to prevent the flow of macromolecules, ions, and small solutes through the paracellular space.
Tight junctions mainly comprise claudin and occludin transmembrane proteins, each with four membrane-spanning alpha-helices.
Rows of claudins and occludins polymerize on the membrane, forming a network of sealing strands.
These strands attach to similar strands of proteins on the adjacent cell by their extracellular loops, thus holding the two membranes together.
On the cytoplasmic side, the C-terminal tails of these proteins associate with the PDZ domains of large scaffold proteins called zonula occludens or ZO.
The ZO proteins have multiple protein-binding domains and can thus bind claudins, occludins, actin, and other ZO proteins, forming a mesh that organizes and stabilizes these sealing strands.
In addition to sealing the paracellular space, tight junctions also prevent the lateral movement of proteins, such as glucose transporters, along the membrane. This helps localize these proteins to the apical surface of the intestinal epithelium for glucose absorption.
Tight junctions are molecular seals between cells that prevent the leaking of fluids, ions, and other small solutes across cavities and compartments in multicellular organisms. They are mainly composed of claudin and occludin transmembrane proteins, and other proteins such as tricellulin and JAM (junctional adhesion molecule). All these proteins are 4-pass transmembrane proteins, except JAM, which is a single-pass transmembrane protein belonging to the immunoglobulin superfamily. The extracellular domains of these tight junction proteins interact with those on the adjacent cell membrane, thus bringing together and sealing the two adjacent cells.
Selective Permeability of Tight Junctions
There are multiple isoforms of the transmembrane claudin, with up to 24 different types expressed in humans. The diversity of the claudin protein confers selective permeability to different tight junctions. For example, claudin-16, expressed in the kidney epithelium increases permeability to magnesium ions, thereby allowing their reuptake from the blood during filtration. In contrast, the claudin-5 expressed in the endothelial cells of the brain capillaries selectively decreases ion permeability across the blood-brain barrier.
Tricellular Junctions
In addition to sealing gaps between two cells, tight junctions also seal the gaps formed at the junction of three cells - a tricellular junction. The structure of tricellular junctions was first observed in the 1970s using freeze-fracture electron microscopy. At these junctions, the sealing strands are oriented perpendicularly to the strands of the bicellular tight junctions. The tricellular contact point thus forms a narrow vertical tube about 10nm diameter, that controls the paracellular movement of molecules.
Tricellulin was the first protein identified to concentrate at these tricellular junctions. It shares sequence homology with the occludin proteins and exhibits four isoforms in humans. Interestingly, mutations in the tricellulin gene, TRIC, are shown to cause hearing impairment, demonstrating its importance in maintaining tight seals such as those required in the organ of Corti - a structure in the inner ear.
In organs such as kidneys and intestines, the epithelial cells are sealed together with tight junctions to prevent the flow of macromolecules, ions, and small solutes through the paracellular space.
Tight junctions mainly comprise claudin and occludin transmembrane proteins, each with four membrane-spanning alpha-helices.
Rows of claudins and occludins polymerize on the membrane, forming a network of sealing strands.
These strands attach to similar strands of proteins on the adjacent cell by their extracellular loops, thus holding the two membranes together.
On the cytoplasmic side, the C-terminal tails of these proteins associate with the PDZ domains of large scaffold proteins called zonula occludens or ZO.
The ZO proteins have multiple protein-binding domains and can thus bind claudins, occludins, actin, and other ZO proteins, forming a mesh that organizes and stabilizes these sealing strands.
In addition to sealing the paracellular space, tight junctions also prevent the lateral movement of proteins, such as glucose transporters, along the membrane. This helps localize these proteins to the apical surface of the intestinal epithelium for glucose absorption.
From Chapter 29:
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29.11 : Tight Junctions
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