Receptor-mediated endocytosis is highly specific

Receptor-mediated endocytosis is used by animal cells to capture specific macromolecules from the cell’s environment. This process depends on receptor proteins, which are proteins that can bind to specific molecules within the cell or in the cell’s external environment. In receptor-mediated endocytosis, the receptors are integral membrane proteins located at particular regions on the extracellular surface of the cell membrane. These membrane regions are called coated pits because they form slight depressions in the cell membrane and their cytoplasmic surfaces are coated by other proteins, such as clathrin. The uptake process is similar to that in phagocytosis.

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When a receptor protein binds to its specific ligand (in this case, the macromolecule to be taken into the cell), its coated pit invaginates and forms a coated vesicle around the bound macromolecule. The clathrin molecules strengthen and stabilize the vesicle, which carries the macromolecule away from the cell membrane and into the cytoplasm (Figure 6.17). Once inside, the vesicle loses its clathrin coat and may fuse with a lysosome, where the engulfed material is digested (by the hydrolysis of polymers to monomers) and the products are released into the cytoplasm. Because of its specificity for particular macromolecules, receptor-mediated endocytosis is an efficient method of taking up substances that may exist at low concentrations in the cell’s environment.

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Figure 6.17 Receptor-Mediated Endocytosis The receptor proteins in a coated pit bind specific macromolecules, which are then carried into the cell by a coated vesicle.

Receptor-mediated endocytosis is the method by which cholesterol is taken up by most mammalian cells. Water-insoluble cholesterol and triglycerides are packaged by liver cells into lipoprotein particles. Most of the cholesterol is packaged into a type of lipoprotein particle called low-density lipoprotein, or LDL, which is circulated via the bloodstream. When a particular cell requires cholesterol, it produces specific LDL receptors, which are inserted into the cell membrane in clathrin-coated pits. Binding of LDLs to the receptor proteins triggers the uptake of the LDLs via receptor-mediated endocytosis. Within the resulting vesicle, the LDL particles are freed from the receptors. The receptors segregate to a region that buds off and forms a new vesicle, which is recycled to the cell membrane. The freed LDL particles remain in the original vesicle, which fuses with a lysosome. There, the LDLs are digested and the cholesterol made available for cell use.

In healthy individuals, the liver takes up unused LDLs for recycling. People with the inherited disease familial hypercholesterolemia have a deficient LDL receptor in their livers. This prevents receptor-mediated endocytosis of LDLs, resulting in dangerously high levels of cholesterol in the blood. The cholesterol builds up in the arteries that nourish the heart and causes heart attacks. In extreme cases where only the deficient receptor is present, children and teenagers can have severe cardiovascular disease.