Endocytosis is a type of active transport that moves particles, such as large molecules, parts of cells, and even whole cells, into a cell. There are different variations of endocytosis, but all share a common characteristic: the plasma membrane of the cell invaginates, forming a pocket around the target particle. The pocket pinches off, resulting in the particle being contained in a newly-created intracellular vesicle formed from the plasma membrane.
Phagocytosis (the condition of “cell eating”) is the process by which large particles, such as cells or relatively large particles, are taken in by a cell. For example, when microorganisms invade the human body, a type of white blood cell called a neutrophil will remove the invaders through this process, surrounding and engulfing the microorganism, which is then destroyed by the neutrophil (Figure 1).
In preparation for phagocytosis, a portion of the inward-facing surface of the plasma membrane becomes coated with a protein called clathrin, which stabilizes this section of the membrane. The coated portion of the membrane then extends from the body of the cell and surrounds the particle, eventually enclosing it. Once the vesicle containing the particle is enclosed within the cell, the clathrin disengages from the membrane and the vesicle merges with a lysosome for the breakdown of the material in the newly-formed compartment (endosome). When accessible nutrients from the degradation of the vesicular contents have been extracted, the newly-formed endosome merges with the plasma membrane and releases its contents into the extracellular fluid. The endosomal membrane again becomes part of the plasma membrane.
A variation of endocytosis is called pinocytosis. This literally means “cell drinking” and was named at a time when the assumption was that the cell was purposefully taking in extracellular fluid. In reality, this is a process that takes in molecules, including water, which the cell needs from the extracellular fluid. Pinocytosis results in a much smaller vesicle than does phagocytosis, and the vesicle does not need to merge with a lysosome (Figure 2).
Potocytosis, a variant of pinocytosis, is a process that uses a coating protein, called caveolin, on the cytoplasmic side of the plasma membrane, which performs a similar function to clathrin. The cavities in the plasma membrane that form the vacuoles have membrane receptors and lipid rafts in addition to caveolin. The vacuoles or vesicles formed in caveolae (singular caveola) are smaller than those in pinocytosis. Potocytosis is used to bring small molecules into the cell and to transport these molecules through the cell for their release on the other side of the cell, a process called transcytosis.
A targeted variation of endocytosis, known as receptor-mediated endocytosis, employs receptor proteins in the plasma membrane that have a specific binding affinity for certain substances (Figure 3). In receptor-mediated endocytosis, as in phagocytosis, clathrin is attached to the cytoplasmic side of the plasma membrane. If uptake of a compound is dependent on receptor-mediated endocytosis and the process is ineffective, the material will not be removed from the tissue fluids or blood. Instead, it will stay in those fluids and increase in concentration. Some human diseases are caused by the failure of receptor-mediated endocytosis. For example, the form of cholesterol termed low-density lipoprotein or LDL (also referred to as “bad” cholesterol) is removed from the blood by receptor-mediated endocytosis. In the human genetic disease familial hypercholesterolemia, the LDL receptors are defective or missing entirely. People with this condition have life-threatening levels of cholesterol in their blood, because their cells cannot clear LDL particles from their blood.
Although receptor-mediated endocytosis is designed to bring specific substances that are normally found in the extracellular fluid into the cell, other substances may gain entry into the cell at the same site. Flu viruses, diphtheria, and cholera toxin all have sites that cross-react with normal receptor-binding sites and gain entry into cells.