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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 i…
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