17.6: Endocytosis and Exocytosis

Endocytosis internalizes extracellular molecules (e.g., proteins), insoluble particles, or even microorganisms. The main pathways of endocytosis are phagocytosis, pinocytosis, and receptor mediated endocytosis. Pinocytosis of molecules is nonspecific. Phagocytosis is also nonspecific, internalizing large structures (e.g., bacteria and food particles). In contrast, receptor-mediated endocytosis is specific for substances recognized by a cell-surface receptor. Some endocytotic processes are even used to recycle membrane components. Exocytosis is the secretion of large molecules like digestive enzymes and peptide or polypeptide hormones, each of which must exit the cell to the extracellular fluid or circulation. Exocytotic pathways also deliver membrane proteins to the cell surface, either new or to replace older, worn-out proteins.

17.6.1 Endocytosis

Figure 17.13: Illustration of three main kinds of endocytosis, routes/mechanisms of import of extracellular materials into cells.

From left to right in Figure 17.13:

1. Phagocytosis (above left): phagocytes extend pseudopodia by evagination of the cell membrane. The pseudopodia of amoeba (and amoeboid cells generally) engulf particles of food, which end up in digestive vesicles (phagosomes) inside the cytosol. Phagocytes are a class of white blood cells that are part of our immune system. They engulf foreign particles that must be eliminated from the body. A lysosome fuses with the phagosome, after which inactive hydrolytic enzymes stored in the lysosomes are activated. The result is the digestion of the engulfed particles. Phagocytosis begins upon contact between the outer cell surface and those particles.
2. Pinocytosis (above center): pinocytosis is a nonspecific, more-or-less constant pinching off of small vesicles that engulf extracellular fluid containing solutes; they are too small to include significant particulates.
3. Receptor-mediated endocytosis (above right): this kind of endocytosis relies on the affinity of receptors for specific extracellular substances. Upon binding their ligands, the membrane receptors aggregate in differentiated regions of plasma membrane called coated pits. The coated pits then invaginate and pinch off, forming a coated vesicle, bringing their extracellular contents into the cell. After the coated vesicles deliver their contents to their cellular destinations, their membranes are recycled to the plasma membrane. Receptor-mediated endocytosis is the best understood mechanism for bringing larger substances into cells. The drawings in Figure 7.14 are taken from electron micrographs that illustrate the invagination of coated pits to form clathrin-coated vesicles.

Figure 17.14: Stages of receptor-mediated endocytosis. Receptors at coated pits bind substances to be imported into a cell, triggering the invagination of the pit to form a cytoplasmic vesicle with imported contents. Invagination is mediated by several proteins, including clathrin.

The receptor and coat proteins are clearly visible as larger structures on the inner surfaces of the pits and on the outer surfaces of the clathrin-coated vesicles. Clathrin, a large protein, is the principal protein on the surface of the invaginated, coated pit. Clathrin is linked to specific integral membrane proteins via adaptor protein 1 (AP1, one of several adaptins). AP1 recruits specific cargo proteins to bring into the cell when the coated pits invaginate. Some details of receptor-mediated endocytosis are illustrated below in Figure 17.15.

Figure 17.15: Follow ligand import into a cell by receptor-mediated endocytosis, from receptor binding at, and invagination of a coated pit, to fusion with an early endosome, formation of a sorting vesicle (late endosome), finally becoming a lysosome that digests and release imported material to the cytoplasm.

In the illustration, substances to be internalized bind to membrane receptors that then cluster to form a coated pit. Assisted by dynamin (a GTPase), the coated pits invaginate. The final pinch-off of a coated vesicle requires GTP hydrolysis (not shown). Once internalized, coated vesicles lose their clathrin and associated adaptor-protein coat. Uncoated vesicles fuse with early endosomes to form sorting vesicles (i.e., late endosomes). Sorting vesicles separate imported content from their receptors. The latter are recycled to the membrane. The vesicles that remain are lysosomes, with digestive enzymes that digest (hydrolyze) vesicle contents that are released and recycled in the cytoplasm. Watch live video of fluorescently labeled proteins, the bright spots, entering cells at Receptor-Mediated Endocytosis (watch the two left panels). The uptake of cholesterol bound to low-density lipoprotein (LDL) is a well-known example of receptor-mediated endocytosis (Figure 17.16).

Figure 17.16: A low-density lipoprotein coated with cholesterol

A single LDL phospholipid-protein complex carries as many as fifteen thousand molecules of cholesterol. LDL, sometimes called “bad cholesterol,” is not good for you at high levels, whereas high-density lipoprotein (HDL) is “good cholesterol.” As one gets older, it is important to monitor one’s HDL/LDL ratio; the higher it is, the better!

17.6.2 Exocytosis and the Formation of Protein-Storage Organelles

Maintaining cell size or volume seems to be a built-in task of the receptor-mediated endocytosis machinery, which balances endocytosis with membrane recycling. Exocytosis is also necessary to restore plasma membrane internalized by pinocytosis and phagocytosis, and for eliminating cellular waste products. Exocytosis is also the end point of the process of packaging proteins for secretion, for intracellular storage (e.g., in lysosomes, peroxisomes) and for insertion into the membrane itself. Endocytotic and secretion vesicles form in “opposite directions,” but both share common structural features with the cell membrane, from which one vesicle type is derived and with which the other fuses (respectively). The formation of lysosomes and secretion vesicles starts in the rough endoplasmic reticulum (RER), followed by passage and maturation through Golgi vesicles, as shown in Figure 17.17.

Figure 17.17: Follow protein sorting (traffic) from translation on RER to-and-through Golgi vesicles (lower right and center-right) to either secretion vesicles (upper right) or storage vesicles (e.g., lysosomes, upper left), and the roles of each pathway in exocytosis and endocytosis.

As we have seen, many secretory and membrane proteins are glycoproteins, and their glycosylation begins in the RER. Check the following link to review the process.

291 The Path to Sugar-Coated Cells

A cell often produces many packaged proteins at the same time. This requires sorting each protein to the correct place—extracellular fluids, lysosomes, peroxisomes, other “microbodies,” and of course, membranes themselves. How do they do it? Some representative packaged proteins are listed in Table 17.1.