Explanation of Terms
Endoplasmic Reticulum
The endoplasmic reticulum (ER) is a membrane-bound structure within the cell that is responsible for fundamental cellular functions. It extends throughout the cell, surrounding the nucleus, and forms a complex network. The endoplasmic reticulum can be broadly divided into two types: rough endoplasmic reticulum and smooth endoplasmic reticulum.
The rough endoplasmic reticulum (RER) has a rough appearance due to the presence of ribosomes, which are structures responsible for protein synthesis, attached to its surface. The main function of the RER is to fold, modify, and direct newly synthesized proteins to their appropriate destinations within the cell.
In contrast, the smooth endoplasmic reticulum (SER) lacks ribosomes and has a smooth appearance. The main functions of the SER include synthesis of lipids and steroids, metabolism of carbohydrates, and detoxification of toxins.
The endoplasmic reticulum plays a central role in protein synthesis and lipid metabolism, contributing to the cell’s viability through these processes. Additionally, the endoplasmic reticulum functions as part of the cellular stress response, detecting and correcting abnormalities in protein folding. Such stress responses from the endoplasmic reticulum play a critical role in maintaining the balance between cell survival and cell death.
Ribosomes
Ribosomes are small structures present in the cells of organisms that carry out the process of protein production, known as translation. This process is crucial for the expression of genetic information, where the information encoded in DNA is transcribed into RNA and then translated by ribosomes into proteins.
Ribosomes are composed of two subunits: the large subunit and the small subunit, which are made up of ribosomal RNA (rRNA) and ribosomal proteins. The binding of these two subunits allows ribosomes to function.
The process by which ribosomes synthesize proteins occurs as follows:
- Messenger RNA (mRNA) binds to the small subunit of the ribosome.
- After recognizing a specific sequence (start codon) on the mRNA, the large subunit binds, forming a complete ribosome.
- The ribosome translates the mRNA by moving along it and translating each codon (a sequence of three nucleotides on the mRNA) into the corresponding amino acid. This translation process is facilitated by transfer RNA (tRNA), which is a specialized RNA molecule.
- Once translation is complete, the newly synthesized protein is released from the ribosome and proceeds to carry out its biological function.
Ribosomes exist in various locations within the cell, including free-floating in the cytoplasm and bound to the surface of the rough endoplasmic reticulum or mitochondria. Their location depends on the type of protein being synthesized and its subsequent fate.
Golgi Apparatus
The Golgi apparatus (also known as the Golgi complex or Golgi body) is a membrane-bound structure within the cell that serves as a major site for the modification, sorting, and packaging of newly synthesized proteins and lipids. It is named after Camillo Golgi, an Italian scientist.
The Golgi apparatus is composed of a series of flattened membranous sacs called Golgi vesicles, which stack on top of each other to form the Golgi apparatus as a whole. The Golgi apparatus has two main faces: the cis face (forming face) and the trans face (maturing face). The cis face, located closer to the endoplasmic reticulum, serves as the entry point where newly synthesized proteins and lipids from the endoplasmic reticulum are received. The trans face serves as the exit point where substances are directed to other parts of the cell.
The main processes that occur in the Golgi apparatus include:
- Modification: Proteins and lipids passing through the Golgi apparatus undergo various chemical modifications, such as the addition or modification of sugar chains (glycosylation). These modifications regulate the functions of proteins and lipids.
- Sorting: Modified proteins and lipids undergo a process to determine where they should be directed. These molecules can be sent to other parts within the cell (such as lysosomes or mitochondria), the cell surface, or even released outside the cell.
- Packaging: Proteins and lipids to be transported are encapsulated in vesicles, which serve as transport carriers.
Through these functions, the Golgi apparatus controls protein trafficking within the cell and plays a crucial role in maintaining cellular functions.
Generation of EVs in the Endoplasmic Reticulum and Golgi Apparatus
Exosomes, or extracellular vesicles (EVs), are small vesicular structures that carry information within cells and play important roles in various biological processes, including intercellular communication, growth, development, immune responses, and disease progression. The following sections provide detailed explanations of the two major cellular structures involved in the generation of exosomes: the endoplasmic reticulum and the Golgi apparatus.
First, the generation of exosomes is accomplished through a complex pathway within the cell, involving the endoplasmic reticulum and the Golgi apparatus. The endoplasmic reticulum (ER) plays a role in folding, modifying, and directing newly synthesized proteins to their appropriate destinations within the cell. Specifically, proteins from the endoplasmic reticulum are sent to the Golgi apparatus, where further modifications occur. The Golgi apparatus serves as a site where proteins are ultimately modified and directed to their intracellular or extracellular destinations.
The generation of exosomes starts from the endoplasmic reticulum. Proteins and lipoproteins secreted from the endoplasmic reticulum exit and move towards the Golgi apparatus. During this process, these proteins and lipoproteins are engulfed by endosomes, which are small vesicles within the cell responsible for transporting substances to other parts within the cell.
When endosomes mature, they form a structure called the multivesicular body (MVB). Within the MVB, numerous intraluminal vesicles, which are precursors of exosomes, are formed. These precursors contain various substances, including proteins, lipoproteins, RNA, and other materials to be transported from the cell to the external environment.
Subsequently, the MVB is delivered to the Golgi apparatus. In the Golgi apparatus, the precursors of exosomes from the MVB undergo further modifications and eventually mature into exosomes. The Golgi apparatus plays a crucial role in performing important modifications that influence the shape and function of exosomes, such as adding glycosylation or phosphorylation to proteins.
Once exosomes mature in the Golgi apparatus, they move toward the cell membrane and fuse with it, leading to the release of exosomes into the extracellular space. This process, known as exocytosis, serves as a major means for cells to share information with the external environment.
The generation and release of exosomes serve as important mechanisms for cells to interact with their environment and also open up new possibilities in the diagnosis and treatment of diseases. For example, exosomes are known to carry signals that assist cancer cells in growth and metastasis. Therefore, understanding the generation and function of exosomes can contribute to better understanding these pathological conditions and finding effective ways to treat them.
Understanding the roles of the endoplasmic reticulum and Golgi apparatus is essential to comprehend the generation and function of exosomes. These cellular structures provide the fundamental mechanisms to ensure the proper formation, modification, and release of exosomes. Therefore, research on exosomes needs to focus on these cellular structures and their roles.
The generation of exosomes involves a complex process that includes the endoplasmic reticulum and Golgi apparatus. These cellular structures facilitate the formation and release of exosomes through a series of processes, such as protein folding, modification, and transport. Research on exosomes is still evolving and offers new insights into how these small vesicular structures influence biological activities and participate in the development and progression of diseases.
Exosomes contain informational molecules such as RNA, DNA, and proteins. These molecules are involved in intercellular communication and regulate cell behavior and function. Exosomes are also believed to be involved in the transmission of information from the external environment to cells.
When are microRNAs incorporated into exosomes?
MicroRNAs (miRNAs) included in exosomes are incorporated at the early stages of exosome generation within the endosomes. Specifically, during the formation of endosomes, miRNAs present in the cytoplasm are taken up into the endosomes.
The specific mechanisms by which miRNAs in the cytoplasm are taken up into endosomes are not yet fully understood. However, several possibilities have been suggested based on multiple studies.
- RNA-binding proteins (RBPs): Certain RNA-binding proteins may interact with miRNAs and facilitate their uptake into endosomes. These proteins bind to miRNAs and aid in their incorporation into endosomes.
- Human protein AGO2: The human protein AGO2 is believed to play a role in incorporating miRNAs into endosomes. AGO2 binds to miRNAs and potentially assists in their uptake into endosomes.
- ESCRT (Endosomal Sorting Complex Required for Transport) complex: This complex is involved in endosome maturation and exosome formation. Its involvement in the uptake of miRNAs into endosomes is not fully elucidated, but some studies suggest a connection.
These mechanisms indicate the potential for cytoplasmic miRNAs to be taken up into endosomes, but the detailed processes and their respective roles are still largely unknown. Research on the relationship between exosomes and miRNAs is ongoing, and further elucidation of the mechanisms is expected in the future.
There is an interesting paper reported in 2022. I plan to summarize its contents soon.
miRNAs taken up into endosomes are enclosed within small vesicles called intraluminal vesicles as the endosomes mature and transform into multivesicular bodies (MVBs). These vesicles eventually become exosomes and carry the miRNAs when released into the extracellular space.
It should be noted that the incorporation of specific miRNAs into exosomes is not random, but certain miRNAs are selectively incorporated into exosomes. The selective mechanism for this incorporation is not fully understood, but factors such as specific RNA-binding proteins are believed to be involved.
Therefore, miRNAs are taken up into exosomes during the formation stage of endosomes and are carried within the exosomes as they mature and are released into the extracellular space.
Understanding the mechanisms of exosome production is essential to achieve therapeutic applications of exosomes. However, due to many remaining unknowns, further research is required. I will continue to keep up with advancements in this field.
