Exocytosis: steps

Exocytosis is a cellular process by which small vesicles present inside cells fuse with the cell membrane, thus expelling their contents to the outside of the cell. This is an active process that requires energy both for the transport of the vesicles from their place of manufacture in the Golgi apparatus to the part of the cell membrane where they will be fused, and for the fusion process itself.

This type of biological process occurs in all eukaryotic cells. Exocytosis fulfills different functions in the different types of cells and tissues of which these cells are a part. In addition, it is combined with endocytosis (incorporation into the cell of foreign material), which is the opposite process to exocytosis, to regulate different aspects of cell function.

types of exocytosis

There are two different types of exocytosis:

• constitutive exocytosis
• regulated exocytosis

These two processes differ in the way they are started, as well as in the function they fulfill, and are described below.

constitutive exocytosis

This type of exocytosis is characterized by occurring constantly during the normal life cycle of the cell, without the intervention of extracellular or intracellular signals. All cells in the body carry out this type of exocytosis, which allows the secretion of the substances that make up the extracellular matrix. In addition to this function, constitutive exocytosis allows the plasma membrane to be kept in equilibrium, since it serves to restore the molecules that are part of the membrane and that are lost through the endocytosis process.

regulated exocytosis

Regulated exocytosis is a type of exocytosis controlled by external stimuli. It consists of a mechanism of secretion of different chemical substances, such as neurotransmitters, hormones or other important chemical substances, in response to a stimulus that can be both chemical and electrical.

For example, regulated exocytosis is the mechanism by which neurons release neurotransmitters at the neuronal synapse or neuromuscular junction. This process is generally triggered by an increase in the intracellular concentration of Ca ²⁺ ions , which can be triggered by the action of another neurotransmitter, or by the opening of ion channels due to depolarization of the plasma membrane.

On the other hand, regulated exocytosis is also the mechanism by which pancreatic cells release hormones, such as insulin and glucagon, to regulate blood glucose levels. In these cases, a low concentration of this carbohydrate in the blood, or glycemia, is the chemical stimulus that generates the exocytosis of glucagon-containing vesicles, while a high concentration stimulates the release of insulin.

stages of exocytosis

Stage 1 – Transport of the vesicles

The movement or transport of endoplasmic vesicles is not random but, on the contrary, it is a well-planned and structured process. Once formed in the Golgi apparatus, vesicles are actively transported (with energy expenditure, ATP) by motor enzymes (such as kinesins, dyneins, and myosins) along the microtubules of the cytoskeleton to their final destination. in a particular region of the membrane.

Stage 2 – Anchoring

The anchoring stage consists of the first contact between the vesicle and the endoplasmic face of the cell membrane. Generally, the anchoring process occurs thanks to the coupling between a protein on the outer surface of the vesicle and a receptor on the inner face of the cell plasma membrane. This coupling or anchor ensures that the vesicle is in the right place to release its contents.

Stage 3 – Coupling

Docking refers to a slightly tighter anchor between the vesicle and the membrane which is produced by a set of unknown proteins. In cases of constitutive exocytosis, this is the step that comes just before the fusion of the two membranes and the subsequent release of the vesicle contents into the extracellular space. In contrast, in the case of regulated exocytosis, docking is generally followed by a fourth step that precedes fusion and the culmination of exocytosis.

Stage 4 – Priming

Priming is a step that is only seen in regulated exocytosis. This process consists of preparing the protein machinery that will facilitate the fusion and subsequent release of neurotransmitters or hormones upon receiving the extracellular secretion signal. During this stage, the trimeric complex called SNARE begins to be assembled, which provides a fixed coupling for the vesicle and allows rapid secretion when needed.

Stage 5 – Fusion

The last stage of the exocytosis process is the fusion of the two phospholipid membranes. This fusion in the case of regulated exocytosis is controlled and carried out by the SNARE complex. With the onset of fusion, a pore begins to form that joins the interior of the vesicle with the extracellular space, thus allowing the release of the vesicle contents. In some cases, the fusion is complete, with the entire vesicle membrane becoming part of the cell membrane, including any membrane-associated proteins in the vesicle. In other cases, after the formation of the pore and the release of the contents of the vesicle, the latter separates from the membrane and returns to the cytoplasm.

Function of exocytosis

Exocytosis can fulfill the following functions:

Express receptors on the cell surface

Most of the proteins that the cell possesses are synthesized on the ribosomes that line the rough endoplasmic reticulum (ER), and this includes all proteins associated with the cell membrane such as antigens, receptors, ion channels, transporters, etc. All these proteins are synthesized, modified and associated with the vesicle membrane during their transit from the ER to the Golgi apparatus and, thanks to the fusion with the cell membrane at the end of exocytosis, these proteins end up integrating into said membrane.

Regulate the size and composition of the membrane

As we have just seen, each time a vesicle fuses with the cell membrane, the former provides the latter with all the proteins it contains. However, this is not all that it provides you. In addition to these proteins, exocytosis also supplies the membrane with a number of phospholipids that increase the total area of ​​the cell membrane, making it larger. Since endocytosis does just the opposite, the balance between exocytosis and endocytosis is able to control the size of the cell membrane.

Secrete the substances that make up the extracellular matrix

Many cells must release different substances into the extracellular space to create the right environment for their functioning and to give the different tissues the properties they should have. Many of these substances are secreted by means of constitutive exocytosis.

release neurotransmitters

Neurons communicate with each other using chemical messages in the form of special substances called neurotransmitters. These substances are secreted to stimulate some type of effect, either to excite or inhibit receptor cells, which can be muscle (in which case they seek to contract or relax a muscle), hormone glands (such as the adrenal gland) or other neurons ( in which case they seek to generate or inhibit action potentials). In all of these cases, neurotransmitters are released via regulated exocytosis.

release of hormones

In addition to allowing the release of neurotransmitters that stimulate or inhibit the various hormone glands in the body, exocytosis is also the mechanism by which these same hormones are released. Again, it is a process of regulated exocytosis.

Nutrient transit

The combination of endocytosis and exocytosis allows the cells lining our gut to take up nutrients from digested food in the intestinal lumen, transport them, and ultimately release them into the blood from nearby vessels, so that they can be transported to the rest of the body where they are needed. . While the capture of large nutritive macromolecules is carried out by means of phagocytosis, their release into the bloodstream is carried out by means of exocytosis.

References

CORDIS | European Commission . (2013). CORDIS. https://cordis.europa.eu/article/id/151139-fundamental-mechanisms-of-exocytosis/en

Megías, MPM (2020, April 6). The cell. 5. Vesicular traffic. exocytosis. Atlas of Plant and Animal Histology. https://mmegias.webs.uvigo.es/5-celulas/5-exocytosis.php

Nofal, S. (2007, February 7). Primed Vesicles Can Be Distinguished from Docked Vesicles by Analyzing Their Mobility . Journal of Neuroscience. https://www.jneurosci.org/content/27/6/1386

Pizarro D., J. (2013). Mechanism of exocytosis of insulin granules . MCU. https://1library.co/article/mecanismo-de-exocytosis-de-los-gr%C3%A1nulos-de-insulina.qogendmz

Meaning of Exocytosis . (2017, November 17). Meanings. https://www.meanings.com/exocytosis/

Technology Networks. (2020, May 18). Endocytosis and Exocytosis: Differences and Similarities . https://www.technologynetworks.com/immunology/articles/endocytosis-and-exocytosis-differences-and-similarities-334059