5.5 Vesicular Transport Across Membranes

In addition to moving small ions and molecules through the membrane, cells also need to remove and take in larger molecules and substances like proteins or polysaccharides. Some cells are even capable of engulfing entire unicellular microorganisms. When a cell uptakes and releases large substances, this process requires energy. However, these substances are too large to cross the membrane via carrier or channel proteins. Vesicular, or bulk, transport is the movement of large substances such as polysaccharides and proteins, from one side of a membrane to another via membrane-bound vesicles. Vesicular transport also occurs between organelles within a cell, but this chapter will focus on transport across the plasma membrane. This transport mechanism can be subdivided into two main categories: endocytosis and exocytosis.

Exocytosis

Exocytosis (“exo” = outside) is the cellular process that involves transporting materials from the inside of a cell into the extracellular fluid via the fusion of a vesicle with the membrane. Material within the cell’s endomembrane system (Chapter 4.3) become enveloped in a vesicle, and that vesicle then fuses with the plasma membrane’s interior. This fusion opens the membranous envelope on the cell’s exterior, and the material is expelled into the extracellular space (Figure 5.29). The vesicle membrane then becomes integrated into the plasma membrane, with the vesicle’s luminal (inside) surface becoming the plasma membrane’s extracellular surface.

An example of animal cells releasing molecules via exocytosis include extracellular matrix protein secretion, neurotransmitter secretion (by neurons), peptide hormone secretion (by endocrine cells), the release of digestive enzymes into the gut, and the elimination of waste products. In plant cells, exocytosis is used to secrete enzymes and structural proteins for the cell wall. Exocytosis is regulated by a complex interplay of factors, including changes in the cytosolic calcium concentration, enzyme activity and interactions with proteins in the membrane. These regulations are critical for ensuring that the proper amount of material is secreted at the appropriate time and place, to maintain cellular homeostasis.

Endocytosis

Endocytosis (“endo” = inside/within) is a type of transport in which a cell takes in materials from its surrounding environment by forming a vesicle or vacuole around those materials. The cell’s membrane invaginates, forming a pocket around the target substance(s). The pocket pinches off, resulting in a newly created intracellular vesicle (sometimes also called a vacuole) formed from the membrane (Figure 5.30). There are several subcategories of endocytosis, including phagocytosis, pinocytosis, and receptor-mediated (clathrin-dependent) endocytosis.

Phagocytosis

Phagocytosis (“phago” = eat) involves the internalization of relatively large substances, such as bacteria or debris, by a cell (Figure 5.31A). During phagocytosis, the cell extends pseudopodia (finger-like extensions of the membrane) around a substance, which is driven by actin microfilaments of the cytoskeleton (Chapter 4.5). The pseudopodia fuse with each other to form a phagosome, a vesicle that encloses the substance. This vesicle is then released from the membrane. To digest the engulfed substances, the vesicle must then fuse with a lysosome that contains hydrolytic enzymes that catalyze the degradation of the engulfed substances into smaller components, which can be used by or eliminated from the cell.

The process of phagocytosis is essential for the immune system of many animals, as it helps to remove pathogens and other foreign particles from living systems. 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 the neutrophil then destroys (Figure 5.31A). In addition to its role in the immune system, phagocytosis also plays a role in other cellular processes, such as the internalization of hormones, the removal of dead cells, and the uptake of nutrients. Defects in phagocytosis can result in numerous disorders, including immunodeficiencies and chronic inflammatory diseases.

Pinocytosis

Pinocytosis (“pino” = drink) involves an intake of fluids and whatever solutes are in that fluid, such as components of the extracellular matrix. Pinocytosis results in a much smaller vesicle than phagocytosis, and the vesicle does not need to merge with a lysosome (Figure 5.31B). The process of pinocytosis begins with the formation of small invaginations or the membrane. The invaginations pinch off to form small vesicles, called pinosomes, which then move into the cytosol and fuse with other intracellular vesicles. Pinocytosis is important for the maintenance of cellular hydration and the uptake of essential substances. This mechanism can also be used by some pathogens, like viruses, to enter host cells and establish infections. As a result, the regulation of pinocytosis is critical for maintaining cellular and organismal homeostasis.

Receptor-mediated Endocytosis

Receptor-mediated endocytosis is characterized by the internalization of specific molecules into a cell through the action of receptor proteins in the membrane that have specific binding affinities (Figure 5.31C). In receptor-mediated endocytosis, proteins called clathrin first attach to the membrane’s cytoplasmic side. The process begins with the binding of a specific ligands, such as a hormone or growth factor, to a specific receptor on the cell surface (see Chapter 5.6 for more information about ligands and receptors). The receptor-ligand complex then clusters together with other receptors to form a clathrin-coated invagination which pinches off from the cellular membrane to form a vesicle. The vesicle moves into the cytoplasm and fuses with endosomes to form endocytic vesicles, which sort and direct the internalized molecules to their destination within the cell, such as the lysosome for degradation or the nucleus for regulation of gene expression.

Receptor-mediated endocytosis is also crucial in physiological roles such as hormone regulation, signaling and nutrient uptake. If a compound’s uptake 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. The failure of receptor-mediated endocytosis causes some human diseases. For example, receptor mediated endocytosis removes low density lipoprotein or LDL (or “bad” cholesterol) from the blood. In the human genetic disease familial hypercholesterolemia, the LDL receptors are defective or missing entirely. This condition causes life-threatening levels of cholesterol in their blood since their cells cannot clear LDL particles. While receptor-mediated endocytosis is designed to bring specific standard substances from the extracellular fluid into the cell, other particles, such as pathogens, may enter the cell at the same site. Flu viruses, diphtheria, and cholera toxin all have sites that cross-react with normal receptor-binding sites, which helps them enter host cells.