Endocytosis

Overview
Endocytosis is a process where cells absorb material (molecules such as proteins) from the outside by engulfing it with their cell membrane. It is used by all cells of the body because most substances important to them are large polar molecules, and thus cannot pass through the hydrophobic plasma membrane. The function of endocytosis is the opposite of exocytosis.

Types
The absorption of material from the outside environment of the cell is commonly divided into two processes: phagocytosis and pinocytosis.


 * Phagocytosis (literally, cell-eating) is the process by which cells ingest large objects, such as cells which have undergone apoptosis, bacteria, or viruses. The membrane folds around the object, and the object is sealed off into a large vacuole known as a phagosome.


 * Pinocytosis (literally, cell-drinking). This process is concerned with the uptake of solutes and single molecules such as proteins.


 * Receptor-mediated endocytosis is a more specific active event where the cytoplasm membrane folds inward to form coated pits. These inward budding vesicles bud to form cytoplasmic vesicles.

Endocytosis pathways
There are three types of endocytosis: namely, macropinocytosis, caveolar endocytosis, and clathrin-mediated endocytosis.


 * Macropinocytosis is the invagination of the cell membrane to form a pocket, which then pinches off into the cell to form a vesicle filled with extracellular fluid (and molecules within it). The filling of the pocket occurs in a non-specific manner. The vesicle then travels into the cytosol and fuses with other vesicles such as endosomes and lysosomes.


 * Caveolae consists of the protein caveolin-1 with a bilayer enriched in cholesterol and glycolipids. Caveolae are flask-shape pits in the membrane that resemble the shape of a cave (hence the name caveolae). Uptake of extracellular molecules are also believed to be specifically mediated via receptors in caveolae.


 * Clathrin-mediated endocytosis is the specific uptake of large extracellular molecules such as proteins, membrane localized receptors and ion-channels. These receptors are associated with the cytosolic protein clathrin, which initiates the formation of a vesicle by forming a crystalline coat on the inner surface of the cell's membrane.

Clathrin-mediated endocytosis
The major route for endocytosis in most cells, and the best-understood, is that mediated by the molecule clathrin. This large protein assists in the formation of a coated pit on the inner surface of the plasma membrane of the cell. This pit then buds into the cell to form a coated vesicle in the cytoplasm of the cell. In so doing, it brings into the cell not only a small area of the surface of the cell but also a small volume of fluid from outside the cell.

Vesicles selectively concentrate and exclude certain proteins during formation and are not representative of the membrane as a whole. AP2 adaptors are multisubunit complexes that perform this function at the plasma membrane. The best-understood receptors that are found concentrated in coated vesicles of mammalian cells are the LDL receptor (which removes LDL from the blood circulation), the transferrin receptor (which brings ferric ions bound by transferrin into the cell) and certain hormone receptors (such as that for EGF).

At any one moment, about 25% of the plasma membrane of a fibroblast is made up of coated pits. As a coated pit has a life of about a minute before it buds into the cell, a fibroblast takes up its surface by this route about once every 50 minutes. Coated vesicles formed from the plasma membrane have a diameter of about 100nm and a lifetime measured in a few seconds. Once the coat has been shed, the remaining vesicle fuses with endosomes and proceeds down the endocytic pathway. The actual budding-in process, whereby a pit is converted to a vesicle, is carried out by clathrin assisted by a set of cytoplasmic proteins, which includes dynamin and adaptors such as adaptin.

Coated pits and vesicles were first seen in thin sections of tissue in the electron microscope by Thomas Roth and Keith Porter in 1964. The importance of them for the clearance of LDL from blood was discovered by R. G Anderson, Michael S. Brown and Joseph L. Goldstein in 1976. Coated vesicles were first purified by Barbara Pearse, who discovered the clathrin coat molecule, also in 1976.

Trans-endocytosis
Trans-endocytosis is the biological process where material created in one cell undergoes endocytosis (enters) into another cell. If the material is large enough, this can be observed using an electron microscope. Trans-endocytosis from neurons to glia has been observed using time-lapse microscopy.

Trans-endocytosis also applies to molecules. For example, this process is involved when a part of the protein Notch is cleaved off and undergoes endocytosis into its neighboring cell. Without Notch trans-endocytosis, there would be too many neurons in a developing embryo. Trans-endocytosis is also involved in cell movement when the protein ephrin is bound by its receptor from a neighboring cell.