The endocytic cycle is crucial for the survival of individual cells and multicellular organisms.
Low-density lipoprotein (LDL) originates in the liver and is transported around the body by the blood stream. From there it is taken up by other cells, such as fibroblasts, and degraded: this provides a source of cholesterol for the growth of these other cells. LDL in the blood binds to LDL receptors on the surface of fibroblasts; these receptors concentrate in coated pits (they are about 200x as concentrated here as along the rest of the cell’s plasma membrane) and are internalised when the pit becomes a coated vesicle. The itinerary of the LDL receptor inside the cell is complex, but it spends little time there. Within a fraction of a minute, it has released its LDL cargo and is returned to the cell surface by exocytosis. It is now ready for another round of LDL clearance.
High levels of LDL in the blood are observed in atherosclerosis and associated with the disease; the endocytic cycle reduces LDL through consuming it. This may or may not be useful in regulating increased levels of LDL, although it may have limitations, or not increase at all in the presence of extra LDL molecules.
Transferrin is a plasma protein that is able to combine with iron ions: It is the vehicle with which iron is carried around the body. Free ferric ions are toxic; but cells need iron to build many of their proteins including cytochromes and hemoglobin. Ferric ions are carried in the blood tightly bound to transferrin as ferritransferrin. Dividing cells, which need the iron, gain it by binding the ferritransferrin to transferrin receptors on their surfaces. These receptors also have a high affinity for coated pits. Like the LDL receptor, the transferrin receptor is internalised into a coated vesicle. The iron is released inside the cell and the receptor returned to the cell surface. The route this receptor takes inside the cell appears to be different from that taken by the LDL receptor, because it takes about 10 minutes before it is exocytosed.
Impulses between neurons are transmitted by the release of neurotransmitters at the junction between the two cells, a region called a synapse. This release is effected by exocytosis at the presynaptic terminal. A vesicle full of transmitter, acetylcholine (for example), in the presynaptic terminal fuses with its neighbouring plasma membrane and thereby releases a burst of acetylcholine into the synaptic space. The acetylcholine is rapidly degraded here, but before this happens it activates acetylcholine receptors on the postsynaptic terminal and triggers an electrical impulse in that cell. The membrane added to the presynaptic terminal is recovered by endocytosis and recycled to form fresh vesicles full of neurotransmitter, ready for another cycle of postsynaptic excitation.
Thus, the function of the nervous system is dependent on this endocytic cycle. An example of this dependence is found in fruit flies. A key protein required for endocytosis is dynamin: It assists in budding a coated pit into a cell to form a coated vesicle. Mutations in the dynamin gene in which the activity of the dynamin protein is lost at above-normal temperatures (for the fly) exist: These are called temperature-sensitive mutations. Such mutant flies have the property that, when the fly is brought from its normal 22°C to 30°C, the dynamin function is lost. However, when the flies are cooled to 22°C, it is regained. In other words, in these mutant flies, the endocytic cycle can be turned off at 30°C, and turned back on by cooling. What one observes is that, within seconds of warming to 30°C, the fruit flies become paralysed: They drop out of the air and appear near-dead. On cooling, they slowly get up, flutter their wings and fly away. The endocytic cycle has been temporarily suspended with drastic effects.
Animal cells, such as fibroblasts, as grown in culture in the laboratory are usually stationary; they grow and divide, but rarely move about. They have a normal endocytic cycle: coated pits 'bud in' from all over the cell’s surface in a random fashion and the returned membrane is exocytosed at the cell’s surface, also at random.