Getting extracellular molecules is essential for cell survival. Endocytosis is a mechanism to get into the cell a large amount of molecules. By endocytosis, molecules and particles are enclosed by the plasma membrane, that, once detached from the plasma membrane, form membrane bound compartments within the cell. These compartments fuse with early endosomes, or mature to become early endosomes.
1. Selection of molecules
There are three ways for molecules to be endocytosed: non specifically as a soluble molecule (pynocytosis), specifically recognized and linked to a membrane receptor (receptor mediated endocytosis), and as part of the membrane of an endocytic vesicle or membrane bound compartment. Pinocytosis always happens during endocytosis because there are soluble molecules that enter the membrane bound compartment by passive diffusion. During endocytosis, lipids and proteins of the plasma membrane that form de membrane of the endocytic compartment are also part of the transported molecules.
Receptor-mediated endocytosis fetches specific extracellular molecules by means of receptors found in the plasma membrane (Figure 1). Molecules and small particles, which may be at low concentrations in the extracellular space, are efficiently included into vesicles by this mechanism. Molecules (also known as ligands) are recognized by these receptors, and the ligand-receptor complexes gather at small plasma membrane areas where vesicles are going to be formed. After pinching off from the plasma membrane, vesicles containing a high concentration of ligands are moved away from the plasma membrane within the cell.
Several types of endocytosis have been described: in vesicles, macropinocytosis and phagocytosis (Figure 2).
Endocytosis mediated by clathrin coated vesicles is the main mechanism for incorporating integral proteins and lipids, both located in the plasma membrane, and extracellular molecules with a size smaller than 156 nm, including some viruses. Clathrin coated vesicles are assembled in plasma membrane areas where the cytoplasmic protein clathrin is concentrated, which alternates between the cytosol and the plasma membrane. The clathrin assembling produces vesicles of about 120 nm in diameter. Once the visicle is closed and released into the cytoplasm, the clathrin coat is disassembled, and the vesicle is targeted to early endosomes.
Caveolae are small invaginations (45-80 nm) of the plasma membrane that can be observed in most eukaryotic cells. It is supposed that most caveolae become vesicles. Caveolae membrane contains the protein caveolin, and is enriched in cholesterol. Most vesicles resulting from caveolae fuse with early endosomes. Choleric toxin, folic acid, and other molecules enter the cell by means of caveolae.
There a endocytic pathway that happens when both clathrin and caveolin are inhibited. Furthermore, invaginations and vesicles show a slightly different morphology. It is largely unknown how is the mechanism of vesicle formation and selection of cargoes.
Macropinocytosis is the endocytic mechanism that allows the cell to fetch a large amount of extracellular material. At the surface of the cell, the plasma membrane, together with underlying cytoplasm, can protrude forming large ridges arranged circularly. The crests of these waves fuses together or fall onto the plasma membrane, that results in a large membrane compartment inside the cell known as macropinosome. Macropinocytosis is not just for feeding, as in amoebas, but also is useful for recycling plasma membrane.
Phagocytosis is a type of endocytosis that engulfs large particles, like bacteria, cellular leftovers, and viruses. It is carried out by specialized cell, such as macrophages, neutrophils, and dendritic cells. Phagocytosis begins with the specific recognition of the particle by plasma membrane receptors, that triggers the formation of laminar and pseudopod protrusions from the cell surface to engulf the particle. The cell expansions surround the particles, fuse their ridges and form an inner membrane bound membrane called phagosome , which mature and fuse with lysosomes for particle degradation.
Cheng JPX, Nichols BJ. 2016. Caveolae: one function or many? Trends in cell biology. doi: 10.1016/j.tcb.2015.10.010.
Mayor S. Pagano RE. 2007. Pathways of clathrin-independent endocytosis. Nature reviews in molecular and cell biology. 8:603-612.
Watanabe S, Boucrot E. 2017. Fast and ultrafast endocytosis. Current opinion in cell biology 47:74-71.