Exocytosis

Exocytosis is the cellular process in which intracellular vesicles in the cy­toplasm fuse with the plasma membrane and release or “secretes” their con­tents into the extracellular space. Exocytosis can be constitutive (occurring all the time) or regulated. Constitutive exocytosis is important in trans­porting proteins like receptors that function in the plasma membrane. Reg­ulated exocytosis is triggered when a cell receives a signal from the outside.

Many of the products that cells secrete function specifically for the tis­sue type in which the cells reside or are transmitted to more distant parts of the body. Most of these products are proteins that have gone through rigorous quality control and modification processes in the endoplasmic reticulum and Golgi membranes. It is in the trans-Golgi network, the “downstream” end of the Golgi apparatus, where cellular products are sorted and accumulate in exocytic vesicles.

Mechanisms

The mechanisms controlling regulated exocytosis were largely discovered in the 1990s. Contrary to early ideas, membranes normally do not fuse to­gether spontaneously. This is due to the negative charges associated with the phospholipids that make up the lipid bilayer of the membranes of vesi­cles and organelles.

Membrane fusion requires energy and the interaction of special “adap­tor” molecules present on both the vesicle and plasma membrane. The adapter molecules are highly selective and only allow vesicles to fuse with membranes of particular organelles, thus preventing harm to the cell. Once the appropriate adapter molecules bind to each other (docking), energy stored and released by ATP forms a fusion pore between the vesicle mem­branes and plasma membrane. The contents of the vesicle are released to the exterior of the cell (or the interior of an organelle) as the fusion pore widens. The vesicle ultimately becomes part of the plasma membrane or is recycled back to the cytoplasm.

Purpose of Exocytosis

Many cells in the body use exocytosis to release enzymes or other proteins that act in other areas of the body or to release molecules that help cells communicate with one another. For instance, clusters of a-and P-cells in the islets of Langerhans in the pancreas secrete the hormones glucagon and insulin, respectively. These enzymes regulate glucose levels throughout the body. As the level of glucose rises in the blood, the ^-cells are stimulated to produce and secrete more insulin by exocytosis. When insulin binds to liver or muscle, it stimulates uptake of glucose by those cells. Exocytosis from other cells in the pancreas also releases digestive enzymes into the gut.

Cells also communicate with each other more directly through the prod­ucts that they secrete. For instance, a neuron cell relays an electrical pulse through the use of neurotransmitters. The neurotransmitters are stored in vesicles and lie next to the cytoplasmic face of the plasma membrane. When the appropriate signal is given, the vesicles holding the neurotransmitters must make contact with the plasma membrane and secrete their contents into the synaptic junction, the space between two neurons, for the other neuron to receive those neurotransmitters.

Components of the vesicle and extra neurotransmitter molecules are quickly taken up and recycled by the neuron to form new vesicles that are ready to send another pulse to an adjacent neuron. Neurons need to send many signals each second, which indicates how tight the controls are that regulate exocytosis.

The immune system also uses exocytosis to communicate information between cells. An immune cell can tell a virally infected cell that it must de­stroy itself to preserve other cells around it. A cell that is infected with a virus displays viral by-products on its surface, which is equivalent to the cell turning on red warning lights to attract immune cells.

Immune cells, such as the killer T cells that wander throughout the body, recognize the viral by-products and position themselves very close to the infected cell so that there is very little space between their plasma mem­branes. In a rapid succession, the killer T cells mobilize secretory vesicles filled with enzymes like perforin and granzyme B adjacent to the inner side of their plasma membranes. In response to a signal, the vesicles undergo exocytosis and release their contents. These enzymes then punch holes in the plasma membrane of the infected cell. This causes the cell to undergo self-destruction or apoptosis, also known as programmed cell death, to prevent further spread of the virus.

References

Cooper, Geoffrey M. The Cell: A Molecular Approach, 2nd ed. Sunderland, MA: Sinauer Associates Inc., 2000.

Lodish, Harvey F., et al. Molecular Cell Biology, 4th ed. New York: W. H. Freeman, 2000