What can a cell use vesicles for?

By Pia Skok

A special feature of all eukaryotic cells is that they are compartmentalized. In other words, they are divided into many smaller, membrane enclosed organelles that contain specific molecules and thus perform a specific function.¹ An example of such compartment are vesicles, sacs enclosed by a lipid bilayer. Although they have a very simple structure, they can be extremely diverse. They can be small and spherical or large and irregularly shaped. They are chemically distinct since they enclose a variety of different macromolecules and enzymes as well as have different internal environments that vary in pH. Furthermore, they express different proteins on their surface creating distinct protein coats on the cytosolic part of their membrane.¹ Because of their structural diversity, they can perform various functions that are vital for cells survival including storage, intracellular transport between cell compartments, transport of molecules in and out of the cell as well as creating specialized environments for optimal enzymatic activity. 

The first important function of vesicles in the cell is creating a specialized environment that houses specific enzymes. This allows the vesicle to perform chemical reactions that do not occur anywhere else in the cell. There are two types of vesicles with this function: peroxisomes and lysosomes. 

Peroxisomes are metabolic vesicles with a high concentration of oxidative enzymes in their core. These enzymes oxidise organic substrates (RH2) to form hydrogen peroxide (H2O2). By oxidising complex organic substrates such as twenty or more carbon long fatty acid, they break them down into smaller metabolites that can be used by other organelles. H2O2 that forms as a side product is used by a specific oxidative enzyme catalase to oxidise alcohol allowing its detoxification. These reactions can be observed in Figure 1.¹ Recent studies have shown that peroxisomes also regulate immunity and inflammation during infection, since they break down prostaglandins and leukotrienes, primary modulators of inflammation.²

Figure 1: Oxidation reactions in peroxisomes

RH2 + O2                          R + H2O2
H2O2 + R’H2                                  R’ + 2H2O (catalysed by catalase)

Lysosomes are another group of vesicles that create a specialized environment within the cell for optimal enzymatic activity. Their lumen is highly acidic with pH of around 4.5-5.0, making them well suited for activity of digestive enzymes. They perform a variety of functions including digestion of substances up taken by endocytosis, degradation of dead organelles and regulating metal ion concentration in the cell. Similar to peroxisomes, they are also important in immune responses because they eliminate pathogens that are engulfed by phagocytosis.³

The second important function of vesicles is transport of material in and out of the cell. In other words, vesicles are the basis of endocytosis and exocytosis. 

During endocytosis, the material, that is to be up taken by the cell, is enclosed by the plasma membrane which invaginates and pinches off forming a small endocytic vesicle. If the endocytic vesicle is filled with water and water-soluble substrates, it is called a pinocytic vesicle as it was formed with pinocytosis or cell drinking. An endocytic vesicle can also contain a large particle such as a pathogen and in such case, it is called a phagocytic vesicle. Once endocytic vesicles form, they fuse with each other forming another vesicle called an early endosome. Here, material is sorted: some cargo is recycled and returned back to the plasma membrane directly or via a recycling endosome, while some cargo remains in the early endosome. The early endosome matures into a late endosome, which fuses with the lysosome allowing degradation of its contents.¹

In addition to endocytosis, vesicles are also vital for secretion or exocytosis during which they fuse with the plasma membrane and release their contents into the extracellular environment. All cells perform constitutive secretory pathway, which is continuous and does not require a signal. During this default pathway vesicles that bud off from the Golgi apparatus fuse directly with the plasma membrane releasing material such as extracellular matrix proteins into the external environment. In contrast, during regulated secretory pathway, which is only performed by specialized cells, contents, such as hormones and digestive enzymes, are first stored and concentrated in another type of vesicle called secretory vesicle. These vesicles fuse with the plasma membrane only in response to a specific signal.¹ A specific type of secretory vesicle is a synaptic vesicle, which is filled by a neurotransmitter and fuses with the neuron plasma membrane in response to an action potential.¹

The third important function of vesicles is intracellular membrane transport, during which another type of vesicle called transport vesicle transports cargo between different membrane-bound compartments by continually budding off from one membrane and fusing with another. They can transport molecules from the endoplasmic reticulum to the Golgi apparatus and from the Golgi to lysosomes, secretory vesicles or back to the endoplasmic reticulum. Furthermore, transport vesicles can transport cargo from one side of the cell to another via a process of transcytosis. Such vesicles are important in epithelial cells of the gut lining, because they transfer the substances that were broken down in the gut across the cells and release them into the blood stream from where they can be carried to other cells in the body.¹ Transport vesicles are structurally very diverse: the cytosolic side of each vesicle membrane is surrounded by a specific cage of proteins called a coat. The type of coat that surrounds the vesicle depends on the type of cargo the vesicle is transporting and its destination. For example, a COPII-coated vesicles transport material from endoplasmic reticulum to Golgi, while COPI-coated vesicles travel from Golgi to the endoplasmic reticulum. Therefore, this coat ensures that transport vesicles only take up appropriate molecules and fuse only with the correct target membrane.¹

The last important function of vesicles is storage of important molecules. An example of storage vesicle is GLUT4 storage vesicle, which stores insulin-responsive glucose transporters and is found in fat and muscle cells.⁴ Many storage vesicles are also found in neurons, where they store GM130, a Golgi matrix protein that mediates vesicle tethering at cis-Golgi network. Lack of GM130 storage vesicles can lead to neuron dysfunction and potentially death. Because storage vesicles contain a high concentration of a specific substance, they allow rapid replenishment if the levels of that substance decrease in other parts of the cell.⁵

In conclusion, cells contain many different types of vesicles that perform a large variety of different functions including storage, transport in, out and within the cell as well as creating specialized environments for optimal enzymatic activity. Although scientists have already gathered a lot of information on vesicle structure and function within the cell, there are still many aspects of vesicles that remain unknown. Mechanisms by which vesicles form, how they are regulated and retained and how cargo is selectively incorporated are not yet completely understood.⁴ Therefore, there might be many other functions that vesicles perform that so far remain unknown. 

References:

1. Alberts, B. et al. 2015. Molecular Biology of the Cell. London: W. W. Norton and Company Ltd. 
2. Di Cara, F. et al. 2019. Peroxisomes in Immune Response and Inflammation. [online]. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721249/. [Acessed 28^th Nov 2021]. 
3. Johnson, D. E. et al. 2016. The position of lysosomes within the cell determines their luminal pH. [online]. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792074/. [Acessed 28^th Nov 2021]. 
4. Li, D. T. et al. 2019. GLUT4 Storage Vesicles: Specialized Organelles for Regulated Trafficking. [online]. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747935/. [Acessed 28^th Nov 2021]. 
5. Vitry, S. et al. 2010. Storage Vesicles in Neurons Are Related to Golgi Complex Alterations in Mucopolysaccharidosis IIIB. The American Journal of Pathology, 177 (6). pg. 2984.