RECEPTOR-MEDIATED ENDOCYTOSIS: PROCESS AND FUNCTIONS - BIOLOGY - 2025

The receptor - mediated endocytosis is a cellular phenomenon comprising controlled specific molecules inside the cell entry. The material to be ingested is progressively surrounded by a small portion of the plasma membrane until the entire substance has been covered. Then this vesicle is detached into the cell interior.

The receptors that participate in this process are located on the cell surface in regions called "clathrin-coated depressions."

Source: Alejandro Porto

This type of endocytosis gives the cell a mechanism to discriminate between the substances that enter. Furthermore, it increases the efficiency of the process, compared to non-discriminatory endocytosis.

The opposite concept of endocytosis is exocytosis, and comprises the release of molecules to the external environment of cells.

What is endocytosis?

Eukaryotic cells have the ability to capture molecules from the extracellular environment and include them inside through a process called endocytosis. The term is attributed to researcher Christian deDuve. It was suggested in 1963 and included the ingestion of a wide range of molecules.

The phenomenon occurs as follows: the molecule or material to be entered is surrounded by a portion of the cytoplasmic membrane that is subsequently invaginated. Thus, a vesicle is formed that contains the molecule.

Classification

Depending on the type of material that enters, the endocytosis process is classified into phagocytosis and pinocytosis.

The first one, phagocytosis, consists of the action of ingesting solid particles. This includes large particles such as bacteria, other intact cells, or debris from other cells. In contrast, the term pinocytosis used to describe the ingestion of fluids.

What is receptor-mediated endocytosis?

Receptor-mediated endocytosis is a cellular phenomenon characterized by the entry of molecules into the cell in a selective and controlled manner. The molecules to enter are specific.

As the name of the process indicates, the molecule to be entered is recognized by a series of receptors located on the surface of the cell. However, these receptors are not found randomly across the membrane. In contrast, its physical location is very specific in regions called “clathrin-lined depressions”.

The depressions form an invagination from the membrane, leading to the formation of clathrin-coated vesicles that contain the receptors and their respective bound macromolecules. The macromolecule that binds to the receptor is called a ligand.

After the formation of the small clathrin vesicles, the latter fuse with structures called early endosomes. In this step, the content of the interior of the clathrin vesicle is distributed to different regions. One of them is lysosomes, or they can be recycled in the plasma membrane.

Features

The traditional pinocytosis and phagocytosis processes are of the non-discriminating type. That is, the vesicles will trap any molecule - solid or liquid - that is in the extracellular space and are transported to the cell.

Receptor-mediated endocytosis provides the cell with a very selective mechanism that allows it to discriminate and increase the efficiency of internalization of particles into the cell environment.

As we will see later, the process allows the taking of very important molecules such as cholesterol, vitamin B12 and iron. These last two molecules are used for the synthesis of hemoglobin and other molecules.

Unfortunately, the presence of receptors that mediate endocytosis has been exploited by a series of viral particles to enter the cell - for example the influenza virus and HIV.

Process

To understand how the receptor-mediated endocytosis process occurs, the uptake of cholesterol by mammalian cells has been used.

Cholesterol is a lipid-like molecule with multiple functions, such as modifying the fluidity in cell membranes and as a precursor of steroid hormones related to the sexual function of organisms.

Receptor-mediated endocytosis model: cholesterol in mammals

Cholesterol is a highly insoluble molecule in water. Therefore, its transport occurs inside the bloodstream in the form of lipoprotein particles. Among the most common we find low-density lipoprotein, commonly abbreviated as LDL - acronic from its acronym in English low-density lipoprotein.

Thanks to studies carried out in the laboratory, it was possible to conclude that the entry of the LDL molecule into the cell occurs by binding to a specific receptor on the cell surface located in clathrin-coated depressions.

The interior of endosomes with LDL is acidic, which allows the dissociation of the LDL molecule and its receptor.

After being separated, the destiny of the receptors is to be recycled in the plasmatic membrane, whereas the LDL continues with its transport now in the lysosomes. Inside, LDL is hydrolyzed by specific enzymes, generating cholestarol.

Finally, cholesterol is released and the cell can take it and use it in various tasks where it is required, such as membranes.

What happens when the system fails?

There is a hereditary condition called familial hypercholesterolemia. One of the symptoms of this pathology is high cholesterol levels. This disorder arises from an inability to introduce the LDL molecule from extracellular fluids into cells. Patients exhibit small mutations in the receptors.

After the discovery of the disease, it was possible to identify that in healthy cells there was a receptor responsible for mediating the entry of LDL, which accumulates in specific cellular depressions.

In some cases, patients were able to recognize LDL, but its receptors were not found in lined depressions. This fact led to the recognition of the importance of lined depressions in the endocytosis process.

Clathrin-independent endocytosis

Cells also have pathways that allow endocytosis to be performed without the involvement of clathrin. Among these pathways, molecules bound to membranes and fluids that can be endocytized despite the absence of clathrin stand out.

Molecules that enter this way penetrate using small invaginations called caveolae located in the plasma membrane.

References

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