Endosome

In biology, an endosome is a membrane-bound compartment inside cells, roughly 300-400 nm in diameter when fully mature. Many endocytotic vesicles derived from the plasma membrane are transported to an endosome and fuse with it. Some endocytosed material passes through endosomes on its way to lysosomes. Endosomes are in part responsible for the sorting of endocytosed material before transport to lysosomes. This allows some material to be returned to the plasma membrane.

Many endocytic vesicles originate at the cell surface as clathrin-coated pits. As clathrin assembles under a patch of plasma membrane the clathrin-coated pit soon (about a minute) pinches off from the surface and forms a clathrin-coated endocytotic vesicle. Soon after forming, the clathrin coated vesicles release their associated clathrin and become competent to fuse with early endosomes. Extracellular materials trapped in the endocytic vesicles can either be passed into the endosomal compartment or returned to the surface.

Some materials are specifically endocytosed by receptor-mediated endocytosis. Some extracellular molecules bind to transmembrane receptor proteins that efficiently accumulate in coated pits. One physiologically important example of receptor-mediated endocytosis is the main mechanism by which cholesterol is taken up by cells, particularly liver cells.

In some people the cholesterol receptor is defective, uptake of cholesterol from the blood into liver cells is slow and cholesterol accumulates in the blood. This is thought to be the cause of damage to blood vessel walls as increased cholesterol levels have also observed in cases of atherosclerosis. As the arterial damage may have caused the cholesterol damage, rather than vice versa, it is unlikely to cause this until further evidence is shown. This receptor defect, if it did lead to blood vessel damage, would lead to observations of strokes and heart attacks at a young age.

One great risk with very high LDL levels is that LDL is vulnerable to free radical damage and that damaged LDL molecules could clump together and form arterial blockages, especially if encountering the sticky platelets of already-damaged blood vessel walls.

Short signal peptides have been identified that target certain transmembrane proteins into clathrin-coated pits. A set of proteins called adaptins bind the signal peptides. The signal for the cholesterol receptor is the tetrapeptide Asn-Pro-Val-Tyr.

Microscopy indicates that in some cells the endosomal compartments is a network of membranous tubes and vesicles extending all the way to the cell nucleus. The deep end of the endosomal compartment is called the late endosome compartment. It may take 5-15 minutes for materials to be transported from the cell surface through early endosome compartments and on to the late endosome. The endosomal compartment is usually acidic due to the action of a proton-pumping ATPase of the endosomal membrane. Many receptors involved in endocytosis of extracellular substances change their conformation at low pH and release their bound substance. The empty receptor proteins can then be sorted back to the cell surface.

Some materials that reach the late endosomes are degraded in lysosomes. Parts of the late endosomal compartment may become lysosomes or temporarily fuse with lysosomes in order to transfer endoctosed materials into the lysosomes. In epithelial cells a special process called transcytosis allows some materials to enter one side of a cell and exit from the opposite side. For example, the GI tract of babies can take protective antibody proteins from breast milk and via transcytosis, transport the antibodies into the blood stream.

A cell surface transferrin receptor binds the iron transport protein transferrin in another example of receptor-mediated endocytosis. In the acidic endosome, the iron is released from transferrin and then the iron-free transferrin (still bound the transferrin receptor) returns from the early endosome to the cell surface.