Endocytosis definition, types and Steps.

Endocytosis definition

• Endocytosis is a cellular process by which cells internalize substances from their external environment. 
• The term “Endocytosis” was first proposed by De Duve in 1963.
• Endocytosis is used by all eukaryotic cells to bring materials into the cell from the outside.
• Cells use this mechanism to get the nutrients that are required for their growth and development.
• There are different types of substances which are internalized by endocytosis such as fluids, electrolytes, proteins, and other macromolecules. 
• During endocytosis, a cell takes up solutes (pinocytosis) or particles (phagocytosis) by enclosing them in vesicles pinched off from the plasma membrane.
• Endocytosis occurs regularly in all eukaryotic cells as a mechanism for recycling molecules in the membrane. In addition, some eukaryotic cells have specialized endocytic pathways that allow them to concentrate materials outside the cell before bringing them in. 
• Others use endocytic pathways as a feeding mechanism. 
• The white blood cells also use the Endocytosis process to capture and destroy potential pathogens such as bacteria and protists.
• Endocytosis is not found in either bacteria or archaea; on the contrary, eukaryotic cells use endocytosis to engulf many viruses and other intracellular pathogens.
• There are present three types of endocytosis such as; phagocytosis, pinocytosis, and receptor-mediated endocytosis.
• Phagocytosis is also known as “cell eating”, where it involves the intake of solid material or food particles. 
• Pinocytosis, also known as”cell drinking”, involves the intake of molecules dissolved in fluid. 
• Receptor-mediated endocytosis performs the intake of molecules based upon their interaction with receptors on a cell’s surface.
• To perform the endocytosis process, the substances must be enclosed inside a vesicle composed from the cell (plasma) membrane.

Basic Steps of Endocytosis

The following steps are involved in the Endocytosis process;

1. The plasma membrane of the cell gets folded inward (invaginates) to form a cavity. This cavity contains extracellular fluid, dissolved molecules, food particles, foreign matter, pathogens, or other substances.
2. Next, the plasma membrane starts to fold back on itself until the edges of the in-folded membrane meet as a result, it will trap the fluid inside the vesicle. Some cells develop long channels which are extended from the membrane deep into the cytoplasm.
3. After the fusion, the vesicle is pinched off from the membrane. The internalized vesicle is then processed by the cell.

Types of Endocytosis

There are present three types of Endocytosis such as;

1. Phagocytosis
2. Pinocytosis
3. Receptor-Mediated Endocytosis or Clathrin-Mediated Endocytosis

Phagocytosis

• It is also known as “cell eating.”
• It is a type of endocytosis pathway, which involves the engulfing of large particles or cells.
• This pathway was first described by Canadian physician William Osler (1876).
• Body’s immune cells use this process to get rid of bacteria, cancer cells, virus-infected cells, or other harmful substances.
• Phagocytosis involves the use of protrusions from the cell surface to surround and engulf particulates. 
• The endocytic vesicles formed by phagocytosis are called phagosomes.
• Later the ingested material within the phagosome is processed by cellular enzymes. 
• Some organisms like amoebas  use this pathway to obtain food from their environment.

Basic Steps of Phagocytosis

The Phagocytosis process occurs in the following steps;

1. Detection: The first step of Phagocytosis is detection, in this step the phagocyte, first of all, detects the antigen (e.g. bacterium) and then starts to move toward the target cell.
2. Attachment: In the second step of Phagocytosis the phagocyte gets attached to the bacterium with the help of pseudopodia (extensions of the cell). It uses pseudopodia to surround the bacterium.
3. Ingestion: Next, the surrounded bacterium gets enclosed within the vesicle, which is formed when the two edges of pseudopodia membranes fuse. This vesicle is known as phagosome, which is internalized by the phagocyte.
4. Fusion: During this step, the phagosome combines with the lysosome and forms a phagolysosome. This phagolysosome contains different types of digestive enzymes which degrade the bacterium (digest organic material).
5. Elimination: Now, the degraded substances are discharged from the cell by the exocytosis process.

Pinocytosis

• The pinocytosis pathway involves cell drinking, where only fluids and dissolved nutrients are taken into a cell.
• The same basic steps of endocytosis are utilized in pinocytosis to internalize vesicles and to transport particles and extracellular fluid inside the cell.
• After getting into the cell, the vesicle started to fuse with a lysosome. 
• After that, the digestive enzymes within the lysosome started to degrade the vesicle and then release its contents into the cytoplasm for use by the cell. 

Types of Pinocytosis Process

There are two main processes by which Pinocytosis is occurred such as;

1. Micropinocytosis 
2. Macropinocytosis 

Micropinocytosis 

• It involves the formation of small vesicles which are around 0.1 micrometers in diameter.
• It mainly occurs in most types of body cells.
• The small vesicles produce by budding from the cell membrane. 
• The micropinocytotic vesicles are known as caveolae. It was first discovered in blood vessel endothelium. 

Macropinocytosis 

• It involves the formation of larger vesicles which are 0.5 to 5 micrometers in diameter.
• It mainly occurs within white blood cells. 
• In Macropinocytosis the vesicles are formed by plasma membrane ruffles instead of the budding process which occurs in Micropinocytosis.
• The extended portions of the membrane are known as Ruffles. These Ruffles are projected within the extracellular fluid and then fold back on themselves. In doing so, the cell membrane scoops up the fluid, forms a vesicle, and pulls the vesicle into the cell.

Receptor-Mediated Endocytosis or Clathrin-Mediated Endocytosis

• Cells used this Receptor-mediated endocytosis process for selective internalization of specific molecules.
• Before internalized these molecules get attached to particular receptors on the cell membrane. These clatherine protein-coated membrane receptors are mainly found in regions of the plasma membrane, they are also known as clatherine-coated pits.
• After the binding of the specific molecule to the receptor, the pit areas are internalized and clatherine-coated vesicles are developed.
• After fusing with early endosomes (membrane-bound sacs that help sort internalized material), the clatherine coating is detached from the vesicles and the contents are released into the cell. 

Basic Steps of Receptor-mediated Endocytosis

• First of all the specific molecule binds to a receptor on the plasma membrane.
• After that, the molecule-bound receptor moves along the membrane towards the region containing a clatherine-coated pit.
• After reaching the clatherine-coated pit,  the pit region develops an invagination that is internalized by endocytosis.
• A clatherine-coated vesicle is developed. It encapsulates the ligand-receptor complex and extracellular fluid.
• Within the cytoplasm, the clatherine-coated vesicle fuses with an endosome and the clatherine coating is removed.
• After that, the receptor is enclosed within a lipid membrane and recycled back to the plasma membrane.
• If not recycled, the specified molecule remains in the endosome and the endosome fuses with a lysosome.
• The specified molecule is degraded by the Lysosomal enzymes and delivers the desired contents to the cytoplasm.

Main components

The endocytic pathway of mammalian cells is made up of various membrane compartments that internalise molecules from the plasma membrane and either recycle them back to the surface (as in early endosomes and recycling endosomes) or sort them for destruction (as in late endosomes and lysosomes). The primary endocytic pathway components are:

• Early endosomes are the initial endocytic pathway compartment. Early endosomes are frequently located at the cell’s periphery and receive the majority of vesicles from the cell surface. They feature a tubulo-vesicular structure (vesicles up to 1 m in diameter with linked tubules of around 50 nm in diameter) and a pH that is slightly acidic. These are primarily sorting organelles in which many endocytosed ligands separate from their receptors due to the acidic pH of the compartment and from which many receptors recycle to the cell surface (via tubules). It is also the site of sorting into the transcytotic pathway to later compartments (such as late endosomes or lysosomes) via transvesicular compartments (such as multivesicular bodies or endosomal carrier vesicles).
• Late endosomes often receive endocytosed material en route to lysosomes from early endosomes in the endocytic pathway, trans-Golgi network (TGN) in the biosynthetic pathway, and phagosomes in the phagocytic pathway. Lysosomal membrane glycoproteins and acid hydrolases, which are characteristic of nucleosomes, mitochondria, and mRNAs, are frequently found in late endosomes. They are acidic (about pH 5.5) and are part of the mannose-6-phosphate receptor trafficking pathway. It is believed that late endosomes mediate a final series of sorting events prior to the transfer of material to lysosomes.
• Lysosomes are the terminal organelle of the endocytic pathway. Their primary job is to degrade cellular waste, lipids, carbohydrates, proteins, and other macromolecules into simple chemicals. They are then returned to the cytoplasm as new components for cell construction. To achieve this, lysosomes utilise over 40 distinct types of hydrolytic enzymes, all of which are produced in the endoplasmic reticulum, modified in the Golgi apparatus, and operate in an acidic environment. A lysosome has an estimated pH of 4.8 and appears as huge vacuoles (1-2 m in diameter) with electron dense material under electron microscopy (EM). There is an abundance of lysosomal membrane proteins and active lysosomal hydrolases, but no mannose-6-phosphate receptor. In general, they are considered the primary hydrolytic compartment of the cell.

Endocytosis Process Image

Endocytosis. For example, coronavirus SARS-CoV-2 binds to the ACE2 receptor of the epithelial cell.

Endocytosis Process Animation

Endocytosis Video

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