EXOCYTOSIS: PROCESS, TYPES, FUNCTIONS AND EXAMPLES - BIOLOGY - 2025

The exocytosis is a process whereby material ejected out of the cell cytoplasm through the cell membrane. It occurs through vesicles found inside the cell, called exosomes, which fuse with the plasma membrane and release their content to the external environment. The reverse process is called endocytosis.

Like endocytosis, it is a process unique to eukaryotic cells. The functions of endocytosis and exocytosis need to be in a dynamic and precise balance for the cell membrane to maintain the size and composition that characterize it.

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Exocytosis occurs in the cell in the first instance to eliminate substances that are not digestible by the digestive machinery and that entered it during the endocytic process. In addition, it is a mechanism used for the release of hormones at different cellular levels.

Exocytosis can also transport substances across a cell barrier, which involves the coupling of processes of entry and exit into the cell.

A substance can be captured from one side of a blood vessel wall through the process of pinocytosis, mobilized through the cell, and released on the other side through exocytosis.

What are exosomes?

Exosomes are small membrane vesicles of varied origin that are secreted by most cell types and are believed to play important roles in intercellular communication. Although exosomes were only recently described, interest in these vesicles has increased dramatically in recent years.

This discovery sparked renewed interest in the general field of secreted membrane vesicles, involved in the modulation of intercellular communications.

Exosomes were initially viewed as highly specific cellular organelles with material discarded by the cell because they had unwanted molecular components or "metabolic junk." They were also seen as a symbol of cell death because they carried waste substances.

However, after the finding that they contain proteins, lipids and genetic material (such as molecules involved in regulation, including mRNA and microRNA), it was concluded that they can affect cells in a more complex way.

Process

In the same way as endocytosis, the cellular secretion process requires energy in the form of ATP, since it constitutes an active process. The Golgi apparatus plays a fundamental role in exocytosis, since the membrane that packages the materials destined for cellular secretion is broken down from it.

The intracellular transport vesicles originate from the Golgi apparatus, moving with their content through the cytoplasm, along the cytoplasmic microtubules, towards the cell membrane, fusing to it and releasing their content to the extracellular fluid.

Endocytosis and exocytosis maintain a balance in the cell that allows the dimensions and properties of the plasma membrane to be preserved. Otherwise, the membrane of a cell would change its dimensions when being extended by the addition of the membrane of the excretory vesicles that are added to it.

In this way, the excess membrane added in exocytosis is integrated again by endocytosis, returning this membrane through the endocytic vesicles to the Golgi apparatus, where it is recycled.

Exosomes not originating from the Golgi apparatus

Not all material destined for exocytosis comes from the trans network of the Golgi apparatus. Part of this comes from early endosomes. These are cellular organelles specialized in receiving the vesicles formed during the endocytosis process.

Within these, after being fused with an endosome, part of the content is reused and transported to the cell membrane by means of vesicles that form in the endosome itself.

On the other hand, in the presynaptic terminals, neurotransmitters are released in independent vesicles to accelerate nerve communication. The latter are often constitutive exocytosis vesicles described below.

Types

The exocytosis process can be constitutive or intermittent, the latter is also known as regulated exocytosis. Vesicles can come from cellular compartments such as primary endosomes (which also receive endocytic vesicles) or can be produced directly in the trans domain of the Golgi apparatus.

The recognition of proteins towards one pathway of exocytosis or another will be given by the detection of shared signal regions between the proteins.

Constitutive exocytosis pathway

This type of exocytosis occurs in all cells and incessantly. Here, many soluble proteins are continuously expelled to the outside of the cell, and many others are recycled, incorporating themselves into the plasma membrane to accelerate and allow their regeneration, since during endocytosis the membrane is rapidly internalized.

This pathway of exocytosis is not regulated so it is always in process. In goblet cells of the intestine and fibroblasts of connective tissue, for example, exocytosis is constitutive, occurring constantly. Goblet cells constantly release mucus, while fibroblasts release collagen.

In many cells that are polarized in tissues, the membrane is divided into two distinct domains (apical and basolateral domain), which contain a series of proteins related to their functional differentiation.

In these cases, proteins are selectively transported to the different domains by the constitutive pathway from the Golgi trans network.

This is accomplished by at least two types of constitutive secretory vesicles that target directly to the apical or basolateral domain of these polarized cells.

Regulated exocytosis pathway

This process is exclusive to specialized cells for secretion, in which a series of proteins or glandular products are selected by the trans domain of the Golgi apparatus and sent to special secretory vesicles, where they are concentrated and then released to the extracellular matrix when they are receives some extracellular stimulus.

Many endocrine cells that store hormones in secretory vesicles, initiate exocytosis only after recognizing a signal from outside the cell, being an intermittent process.

The fusion of the vesicles to the cell membrane is a common process in various cell types (from neurons to endocrine cells).

Proteins involved in the process of regulated exocytosis

Two families of proteins are involved in the exocytosis process:

• The Rab, which are responsible for the anchoring of the vesicle to the membrane and give specificity to vesicular transport. They are generally associated with GTP in its active form.
• On the other hand, the SNARE effector proteins enable fusion between the membranes. An increase in the concentration of calcium (Ca2 +) inside the cell, functions as a signal in the process.

The Rab protein recognizes the increase in intracellular Ca2 + and initiates the anchoring of the vesicle to the membrane. The area of ​​the vesicle that was fused opens and releases its contents to the extracellular space, while the vesicle fuses with the cell membrane.

Exocytosis "kiss and run"?

In this case, the vesicle that is about to fuse with the membrane does not do so completely, but does so temporarily, forming a small opening in the membrane. This is when the inside of the gallbladder comes into contact with the outside of the cell, releasing its contents.

The pore closes immediately afterwards and the gallbladder remains on the cytoplasmic side. This process is closely tied to the hippocampal synapse.

Features

Cells carry out the process of exocytosis, to transport and release large, lipophobic molecules as proteins synthesized in cells. It is also a mechanism by which waste that remains in the lysosomes after intracellular digestion is shed.

Exocytosis is an important intermediary in the activation of proteins that remain stored and inactive (zymogens). Digestive enzymes, for example, are produced and stored, activating after being released from cells into the intestinal lumen through this process.

Exocytosis can also act as a transcytosis process. The latter consists of a mechanism that allows some substances and molecules to pass through the cytoplasm of a cell, passing from an extracellular region to another extracellular region.

The movement of the transcytosis vesicles depends on the cell cytoskeleton. Actin microfibers have a motor role, while microtubules indicate the direction to be followed by the vesicle.

Transcytosis allows large molecules to pass through an epithelium, remaining unharmed. In this process, babies absorb maternal antibodies through milk. These are absorbed on the apical surface of the intestinal epithelium, and are released into the extracellular fluid.

Exosomes as intercellular messengers

In the immune system, excretory vesicles or exosomes play an important role in intercellular communication. Some cells, such as B lymphocytes, have been shown to secrete exosomes with molecules essential for the adaptive immune response.

Said exosomes also present MHC-peptide complexes to specific T cells of the immune system.

Dendritic cells similarly secrete exosomes with MHC peptide complexes, which induce antitumor immune responses. Various studies have indicated that these exosomes are excreted by some cells and captured by others.

In this way, important molecular elements such as antigens or peptide complexes are added or obtained that increase the range of antigen presenting cells.

Likewise, this information exchange process increases the efficiency of the induction of immune responses, or even negative signals that lead to the death of the target cell.

Some attempts have been made to use exosomes as a type of cancer therapy in humans, with the purpose of transmitting information that modulates tumor cells, leading them to apoptosis.

Examples

In organisms such as protozoa and sponges that have intracellular digestion, nutritive substances are absorbed by phagocytosis and non-digestible debris is removed from the cell by exocytosis. However, in other organisms, the process becomes more complex.

Exocytosis in vertebrates

In mammals, during the formation of erythrocytes, the nucleus, together with other organelles, contracts, becoming vestigial. This is then wrapped in a vesicle and expelled from the cell through the process of exocytosis.

In contrast, many endocrine cells that store hormones in excretory vesicles, initiate exocytosis only after recognizing a signal from the outside of the cell, being an intermittent or regulated exocytosis process.

Exocytosis plays important roles in some response mechanisms in the body, such as inflammation. This response mechanism is mainly mediated by histamine, present in mast cells.

When histamine is released to the outside of the cell through exocytosis, it allows the dilation of blood vessels, making them more permeable. In addition, it increases the sensitivity in the sensing nerves, causing the symptoms of inflammation.

Exocytosis in neurotransmitter release

Neurotransmitters move rapidly through the synaptic junction, binding to receptors on the postsynaptic portion. The storage and release of neurotransmitters is carried out by a multi-step process.

One of the most relevant steps is the union of the synaptic vesicles to the presynaptic membrane and the release of their content by exocytosis to the synaptic cleft. The release of serotonin by neuronal cells occurs in this way.

In this case, the mechanism is triggered by cellular depolarization, which induces the opening of calcium channels, and once it enters the cell, it promotes the expulsion mechanism of this neurotransmitter through the excretory vesicles.

Exocytosis in other eukaryotes

Exocytosis is the means by which membrane proteins implant themselves into the cell membrane.

In plant cells, exocytosis is used in the constitution of cell walls. Through this process, some proteins and certain carbohydrates that have been synthesized in the Golgi apparatus are mobilized to the outside of the membrane, to be used in the construction of said structure.

In many protists with an absent cell wall, there are contractile vacuoles that act as cell pumps. They recognize excess water inside the cell and expel it outside it, providing an osmotic regulation mechanism. The function of the contractile vacuole is carried out as a process of exocytosis.

Some viruses use exocytosis

Enveloped DNA viruses use exocytosis as a release mechanism. After multiplication and assembly of the virion in the host cell and once it has acquired an enveloping membrane of the nucleoprotein, it leaves the cell nucleus, migrating to the endoplasmic reticulum and from there to the expulsion vesicles.

Through this release mechanism, the host cell remains undamaged, in contrast to many other plant and animal viruses that cause cellular autolysis in order to exit these cells.

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