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5.13: Receptor-mediated Endocytosis
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Biology

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Receptor-mediated Endocytosis
 
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5.13: Receptor-mediated Endocytosis

Overview

Receptor-mediated endocytosis is a process through which bulk amounts of specific molecules can be imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle and give it its round form.

Clathrin-Mediated Endocytosis of LDL

One well-characterized example of receptor-mediated endocytosis is the transport of low-density lipoproteins (LDL cholesterol) into the cell. LDL binds to transmembrane receptors on the cell membrane. Adapter proteins allow clathrin to attach to the inner surface of the membrane. These protein complexes bend the membrane inward, creating a clathrin-coated vesicle inside the cell. The neck of the endocytic vesicle is pinched off from the membrane by a complex of the protein dynamin and other accessory proteins.

The endocytic vesicle fuses with an early endosome, and the LDL dissociates from the receptor proteins due to a lower pH environment. Empty receptor proteins are separated into transport vesicles to be re-inserted into the outer cell membrane. LDL remains in the endosome, which binds with a lysosome. The lysosome provides digestive enzymes that break up LDL into free cholesterol that can be used by the cell.

Roles of Receptor-Mediated Endocytosis

There are multiple functions that endocytosis can serve. In the example above, endocytosis is used to take resources (LDL) into the cell. Similarly, iron is taken into the cell via endocytosis of transferrin—an iron-binding protein—at the cell surface, where it binds to the transferrin receptor (TfR). Similar to LDL endocytosis, a clathrin-coated vesicle is formed to bring the transferrin into the cell. In the early endosome, a pH decrease allows the dissociation of iron from transferrin. Transferrin, however, remains bound to the TfR. When the receptor is sent back to the cell surface to be reused, the transferrin protein (without iron) is released back into the extracellular environment.

Receptor-mediated endocytosis is also used to regulate cell signaling. One of the primary ways that signal receptors are regulated is sequestration, which involves bringing receptors inside the cell using endocytosis. Some receptors are stored within vesicles until they are needed again, and some are degraded by proteolytic enzymes. Other signaling pathways require receptor-mediated endocytosis to allow signal transduction (i.e., passing the signal into the cell) to take place.

Types of Receptor-Mediated Endocytosis

The endocytosis of LDL is an example of clathrin-mediated endocytosis. There are also alternative pathways for endocytosis, of which caveolin is the most-studied. Unlike clathrin, which binds to the surface, caveolin inserts itself into the lipid bilayer. The result is similar, however, as caveolin causes a curve in the membrane that allows an endocytic vesicle to form that pinches off from the membrane.

Use of Receptor-Based Endocytic Pathways by Pathogens

Some bacteria and viruses can invade host cells by hijacking the host’s native receptors. Influenza virus can invade host cells using clathrin-mediated and other endocytic pathways. The virus binds to receptors on the cell surface, gaining access to the host cell, where it later escapes from the endosome.

Some pathogens release toxins that bind to host receptors to trick the cell into taking them inside. The bacterium Bacillus anthracis produces the toxin known as anthrax; this toxin is capable of binding to receptors, undergoing endocytosis, and then escaping the late endosome to cause necrosis and other clinical symptoms.


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Tags

Receptor-mediated Endocytosis Pinocytosis LDL Low-density Lipoproteins Bad Cholesterol Adapter Proteins Lipids Phosphatidylinositol Phosphates PIPs Conformational Change Cell Surface Cargo Receptors Apo-B Protein Membrane Curvature Clathrin Triskelions Clathrin-coated Pit Membrane Bending Proteins Fusion Proteins Endosomes Cargo Receptors Lower-pH Environment Cholesterol Amino Acids

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