Concept 5.4: Large Molecules Cross Membranes via Vesicles

Macromolecules such as proteins, polysaccharides, and nucleic acids are simply too large and too charged or polar to pass through biological membranes. This is a fortunate property—cellular integrity depends on containing these macromolecules in specific locations. However, cells must sometimes take up or secrete (release to the external environment) intact large molecules. This is done via vesicles, and the general terms for the mechanisms by which cells secrete and take up large molecules or particles are exocytosis and endocytosis (FIGURE 5.8).

Figure 5.8: Endocytosis and Exocytosis Eukaryotic cells use endocytosis (A) and exocytosis (B) to take up and release large molecules and particles. Even small cells can be engulfed via endocytosis.

Exocytosis moves materials out of the cell

Exocytosis is the process by which materials packaged in vesicles are secreted from the cell (see Figure 5.8B). When the vesicle membrane fuses with the cell membrane, an opening is made to the outside of the cell. The contents of the vesicle are released into the environment, and the vesicle membrane is smoothly incorporated into the cell membrane.

In Chapter 4 we encountered exocytosis as the last step in the processing of material engulfed by phagocytosis—the release of undigested materials back to the extracellular environment (see Figure 4.9). Secreted proteins are also transported out of the cell via exocytosis. The proteins are folded and modified in the endoplasmic reticulum and then transported in vesicles to the Golgi apparatus, where they may be further modified. Finally, the proteins are packaged in new vesicles for secretion (see Figure 4.8).

Exocytosis is important in the secretion of many types of substances, including digestive enzymes from the pancreas, neurotransmitters from neurons, and materials for the construction of the plant cell wall. You will encounter these processes in later chapters.

Macromolecules and particles enter the cell by endocytosis

Endocytosis is a general term for a group of processes that bring small molecules, macromolecules, large particles, and even small cells into eukaryotic cells (see Figure 5.8A). The cell membrane invaginates (folds inward), forming a small pocket around materials from the environment. The pocket deepens, forming a vesicle. This vesicle separates from the cell membrane and migrates with its contents to the cell’s interior.

Endocytosis often depends on receptors (see Concept 5.5), which are proteins that bind to specific molecules (their ligands) and then set off specific cellular responses. In endocytosis, the receptors are integral membrane proteins located on the extracellular surface of the cell membrane. Vesicle formation results in the internalization of both the receptor and its ligand, along with other substances present near the site of invagination.

There are three broad types of endocytosis: phagocytosis, pinocytosis, and receptor endocytosis:

• In phagocytosis (“cellular eating”), receptors in the cell membrane recognize a specific ligand on the surface of a large particle or even an entire cell. The binding of the ligand to the receptor causes the phagocytic cell to engulf the particle or other cell. Phagocytosis is restricted to specialized cells; for example, unicellular protists use phagocytosis for feeding, and some white blood cells use phagocytosis to engulf foreign cells and substances. The food vesicle (phagosome) that forms usually fuses with a lysosome, where the vesicle’s contents are digested.

  LINK

  Review the discussion of phagocytosis in Concept 4.3

• Vesicles also form in pinocytosis (“cellular drinking”). However, in this case the vesicles bring fluids and dissolved substances, including proteins, into the cell. Pinocytosis is relatively nonspecific regarding what it brings into the cell. For example, pinocytosis goes on constantly in the endothelium—the single layer of cells that separates a blood capillary from the surrounding tissue. Pinocytosis allows cells of the endothelium to rapidly acquire fluids and dissolved solutes from the blood.
• Receptor endocytosis (also called receptor-mediated endocytosis) is a mechanism for bringing specific large molecules, recognized by specific receptors, into the cell. In recent years it has become clear that receptor endocytosis also plays an important role in cell signaling, which we will discuss in Concepts 5.5 and 5.6. Put simply, receptor endocytosis allows cells to control their internal processes by controlling the location and abundance of each type of receptor on the cell membrane.

Let’s take a closer look at the process of receptor endocytosis.

Receptor endocytosis often involves coated vesicles

In receptor endocytosis, the receptors are often located at particular regions, called coated pits, on the extracellular surface of the cell membrane. These pits form slight depressions in the cell membrane, and their cytoplasmic surfaces are coated by another protein, often clathrin. The uptake process is similar to that in phagocytosis. The clathrin (or other protein) molecules strengthen and stabilize the vesicle (FIGURE 5.9).

Figure 5.9: Receptor Endocytosis The receptor proteins in a coated pit bind specific macromolecules, which are then carried into the cell by a coated vesicle.

Once inside the cell, the vesicle loses its clathrin coat and fuses with a membrane-enclosed compartment called an endosome, where the ligands, receptors, and other substances in the vesicle are separated and sorted. Some of these components are transferred to the lysosome for degradation, while others may be transferred back to the cell membrane. Thus a receptor may be recycled to the cell membrane or degraded in the lysosome, and as we mentioned above, this is an important mechanism by which the cell controls the abundance of each kind of receptor at its surface.

Receptor endocytosis is the way cholesterol is taken up by most mammalian cells. Cholesterol and triglycerides, which have low solubility in water, are packaged by liver cells into lipoprotein particles. Most of the cholesterol is packaged into low-density lipoproteins (LDLs) and circulated via the bloodstream. When a particular cell requires cholesterol, it produces LDL receptors, which are inserted into the cell membrane. The receptors diffuse laterally through the membrane until they become associated with clathrin-coated pits. LDLs bind to the receptors and are taken into the cell via receptor endocytosis. After separation from the receptors, the LDL particles are transferred to the lysosome, where they are broken down and the cholesterol made available for use by the cell.

In healthy individuals, the liver takes up unused LDLs for recycling. People with the inherited disease familial hyper-cholesterolemia have a defective LDL receptor in their livers. This prevents receptor endocytosis of LDLs in the liver, resulting in dangerously high levels of cholesterol in the blood. The cholesterol builds up in the arteries that nourish the heart and causes heart attacks. In extreme cases where only the defective receptor is present, children and teenagers can have severe cardiovascular disease.

Receptor endocytosis also plays an important role in cell signaling, which we will discuss in the following concepts.

We have just introduced the concept of a membrane-bound receptor, which is a key factor in a cell’s interaction with its environment. Let’s look more closely at receptors and how they respond to signals.