Definition of Endocytosis
- Endocytosis is a cellular mechanism by which a cell internalizes substances such as proteins, fluids, electrolytes, microorganisms, and certain macromolecules from its external environment. These substances are subjected to certain processes of decomposition into smaller elements, either for use by the cell or for elimination.
- White blood cells of the immune system are the most common cells that use endocytic mechanisms to remove microbial pathogens from the body. They catch pathogens, break them down and destroy them to eliminate them from the body.
- Endocytosis was first described by Christian de Devu, a Belgian cytologist and biochemist who has received several Nobel Prizes for his role in the discovery of cellular elements such as lysosomes, peroxisomes, endosomes and even mechanisms of cellular exocytosis, including the mechanism of endocytosis.
Process of Endocytosis
- The cell membrane folds into a cavity filled with extracellular fluid, dissolved molecules, food particles, foreign material, pathogens, and / or other substances, a process known as intussusception.
- After invagination, the cell membrane folds back on itself until it forms a uniformly closed membrane around closed molecules and this closed membrane or cavity is called a vesicle. Some cells form extension channels in the cell cytoplasm.
- The formed vesicle is detached from the cell membrane, which is then processed by the cell.
Types of Endocytosis mechanisms
There are three types of endocytosis mechanisms:
- Receptor-Mediated Endocytosis (Clathrin-Mediated Endocytosis)
- Also known as phagocytes; It is the process by which the cell membrane of a cell expands into a particle, enveloping it and trapping it in this folded membrane that forms a phagosome. The material taken up in the phagosome is then processed by cellular enzymes. Phagocytosis is a common mechanism in multicellular organisms by white blood cells (macrophages, monocytes, neutrophils, eosinophils, dendritic cells) to clear pathogens from the system. Some protozoa, such as Entamoeba spp, use phagocytosis to obtain nutrients;
- The mechanism of phagocytosis was first observed by the Canadian physician William Osler (1876).
- Phagocytosis takes place in 5 stages:
- Phagocytic cells recognize the molecule of interest or an antigen and move towards it.
- The phagocyte then attaches to the antigen or target molecule. Phagocytes have the ability to extend their membrane (pseudopodia) to the target particle and surround the pathogenic particle. The pseudopods spread towards each other, trapping the particles.
- The particle is then trapped in the vesicle, which is formed from the expanded pseudopodia which are fused together. The vesicle containing the trapped particles is called a phagosome. It is the vesicle that is digested by the phagocytes.
- The phagosome fuses with the lysosomes of the phagocytes and forms a phagolysosome. Lysosomes have digestive enzymes that break down or digest the materials in the gallbladder.
- The degraded particles are then expelled from the phagocytic cell by exocytosis.
Example of phagocytosis
- A typical example of phagocytosis is the mechanism of immune cells such as macrophages, dendritic cells and neutrophils. Macrophages are the largest phagocytic cells in the immune system. They work by recognizing, attaching, ingesting, digesting, and releasing digested particles from your cytoplasm through exocytosis. Antigens vary and include bacteria, fungi, dust particles, dead cells, etc. Macrophages are the main phagocytic cells of the immune system. They have a pseudopodia membrane. When an antigen is detected, they move towards the antigen and spread their pseudopodia in the direction of the antigen, and devour it. When swallowed, the cell absorbs the antigen and forms a cell vesicle, also called a phagosome. Within the macrophage, the vesicle meets the lysosomes and forms a phagolysosome, which is digested by lysosomal enzymes which break down the particle and then exocytose the cell.
- The adhesion of the particle to phagocytes strongly depends on the chemical nature of the particle. Some bacterial antigens bind directly, and some require a protein component in the blood called opsonin (like antibody supplements) to form a film on the bacterial surface that adheres to phagocytes, a process known as opsonization. Then phagocytes first bind to opsonin for phagocytosis to take place.
- Some encapsulated cell wall bacteria are quite difficult to digest, even with an opsonin. Therefore, once the body has responded to their presence, they must bind to specific antibodies. The phagocytes can then act on the encapsulated bacteria which are bound to the antibody.
- Also known as cell depletion or fluid endocytosis; It is a form of endocytosis in which small particles in extracellular fluids invade the cell through the cell membrane by invagination and form a small vesicle of small molecules or particles that are suspended in a cell. The pinocytic vesicle fuses with the cell endosome to digest the particles.
- Its mechanisms are similar to other endocytic processes, the main difference between pinocytosis and phagocytosis is that in pinocytosis the ingested particles are contained in the extracellular fluids of the cell. The cell membrane envelops the vesicle with liquid particles and transports them to cell lysosomes. The vesicles and lysosomes merge, releasing digestive enzymes from the lysosomes. The enzymes break down the vesicle and release its contents into the cell cytoplasm for use by the cell.
- Sometimes the vesicles do not interact with the lysosomes but move through the cell, fuse with the cell membrane and cause a recycling effect of membrane proteins and lipids.
- Pinocytosis occurs by two mechanisms:
- Micropinocytosis: it is the formation of small vesicles about 0.1 µm in diameter; It takes place in the cells of the body forming tiny budding vesicles in the cell membrane called caveolae. They are located in the endothelium of blood vessels.
- Macropinocytosis – This is the formation of larger vesicles, about 0.5 to 5 µm in diameter; are found in white blood cells; large vesicles are formed by the leaflets of the cell membrane (villi), which are protrusions that extend into extracellular fluids and have the ability to self-fold. By folding, they introduce some of the extracellular fluid and form a vesicle which is inserted into the cell.
Example of pinocytosis:
The absorption or absorption of nutrients in the small intestine.
- This is a type of endocytosis also known as clathrin-mediated endocytosis; It involves the internalization and recycling of receptors used in processes such as signal transmission (G protein receptors and tyrosine kinase), nutrient uptake and the formation of new synaptic vesicles.
- This process is initiated by the accumulation of phosphatidylinositol-4,5-bisphosphate (PIP2) within the cell membrane. The accumulation of PIP2 is due to the catalytic process of phosphoinositide within the plasma membrane. PIP2 accumulates under the effect of phosphoinositide by lipid kinase and hydrolysis of phosphatases. The combination of adapter proteins (AP proteins) with phosphatidylinositol-4,5-bisphosphate (PIP2) results in the binding of a cytosolic protein called clathrin to the gallbladder. This forms clathrin-coated vesicles (CCV).
- Clathrin-coated vesicles (CCV) must penetrate and mature to form clathrin-coated dimples. Clathrin-coated vesicles bind to the cell membrane by recruiting several proteins, including actin-binding proteins, adapter proteins (APs), all of which play an important role in the maturation of vesicles.
- CCV, which contains several receptors bound to ligands and adapter proteins, is then everted in the membrane and matured using the protein Dynamin and cleaved from the cell membrane, forming a clathrin coated depression.
- How are clathrin coated dimples formed? Clathrin-coated vesicles are found in most, if not all cells, and therefore, upon detection of a signal, these vesicles recruit adapter proteins to the plasma membrane which accumulate in the lipid layer of the membrane. cell plasma.
- Adapter proteins build clathrin from vesicles coated with clathrin with actin-binding proteins in cell membrane lipids. Due to the negative charge on the lipid layer, it is attracted to the positive charge on clathrin and forms a concave shape that rises from the membrane and creates holes in the plasma membrane.
- The clathrin in the pits acts as a sensor for signals that activate endocytosis, while the vesicle of the clathrin-coated vesicle is returned to the cell membrane. The cycle between clathrin-coated pits and the formation of clathrin-coated vesicles is continuous as long as there are signal receptors and ligands to activate them.
- The process of receptor-mediated endocytosis includes the following steps:
- The particles (ligands) to be synthesized bind to receptors on the cell membrane. The receptors with the ligands come together to form the coated wells. Then the pits are everted with the help of dynamin proteins, which form a vesicle, and the vesicle is compressed inside the cell membrane. The vesicles then lose clathrin and adapter proteins.
- The uncoated vesicle then fuses with an early endosome to form the late endosome or sorting vesicle. The late endosome secretes the particles within the vesicle, i.e. the ligand receptors, and recycles them to the cell membrane.
- The released particles interact with lysosomes, which contain digestive enzymes that hydrolyze the contents of the vesicles. The digested particles are then released for use by the cell.
- This mechanism of receptor-mediated endocytosis (clathrin-coated endocytosis) can best be used to deliver macromolecules into the cell.
Examples of Clathrin-Mediated Endocytosis
There are two classic examples of clathrin-mediated endocytosis, including
- recycling of iron-bound transferrin
- Receptor-mediated endocytosis is the absorption of low-density lipoprotein (LDL) cholesterol, a complex of phospholipids, proteins, and cholesterol.
Definition of Endocytosis, and Process of Endocytosis