Cells constantly communicate by sending signals and materials to their neighbors. One way they do this is by releasing tiny packages called exosomes, which are small, membrane-bound vesicles created by nearly all cell types. First identified decades ago, exosomes were initially thought to be a method for cells to discard waste. Scientific understanding has since evolved, and they are now recognized as couriers that transport molecular information between cells, influencing the behavior of the recipient.
How Cells Manufacture Exosomes
Exosome production begins in a cellular compartment called an endosome. The process starts when the cell’s outer membrane folds inward, creating an early endosome that acts as a sorting station. As this structure matures, its own membrane buds inward, forming smaller vesicles inside itself. This process creates a multivesicular body (MVB), which contains many tiny intraluminal vesicles (ILVs).
The formation of ILVs is managed by a group of proteins called the Endosomal Sorting Complex Required for Transport (ESCRT). This complex selects specific molecules like proteins and nucleic acids to be packed into the forming vesicles. While this is a primary pathway, cells have other methods for creating these vesicles, ensuring they are deliberately packed with specific cargo.
A fully formed MVB can either travel to a lysosome for its contents to be recycled or move to the cell’s outer edge. If it reaches the edge, the MVB fuses with the plasma membrane. This fusion releases the internal vesicles into the space outside the cell, at which point they are officially called exosomes.
The Cargo Packed Within Exosomes
An exosome’s contents are a direct reflection of the cell that produced it, containing a specific assortment of bioactive molecules. This cargo is categorized into three main types: proteins, lipids, and nucleic acids. The proteins can include enzymes, growth factors, and signaling proteins that trigger responses in recipient cells. Exosomes also carry structural proteins and those involved in their creation, like tetraspanins CD63 and CD81, which are often used as markers for identification.
The lipid bilayer that forms the exosome’s outer shell has a unique composition, often enriched in cholesterol and ceramides that contribute to its stability. This distinct lipid profile helps protect the exosome and its contents as it navigates the extracellular environment. The composition also facilitates the exosome’s interaction with and uptake by a target cell.
Exosomes are also carriers of genetic information in the form of nucleic acids. This includes messenger RNA (mRNA), which can be translated into proteins by the recipient cell, and non-coding RNA, such as microRNA (miRNA). These RNA molecules are regulators of gene expression and can alter the function of the cells that take them up.
Why Cells Release Exosomes
A primary reason cells release exosomes is for intercellular communication. They act as messengers, carrying molecular cargo to recipient cells, which can be nearby or distant. Upon reaching a target cell, an exosome can fuse with the cell’s membrane or be taken inside, delivering its contents. This transfer of proteins and nucleic acids can influence the recipient cell’s behavior by altering gene expression or activating signaling pathways.
Another function of exosome release is cellular waste management. Cells use exosomes to expel unwanted or potentially harmful molecules to maintain internal balance. By packaging these materials into vesicles and sending them away, the cell protects itself from accumulating toxic substances or molecules that are no longer needed.
Exosomes also play a part in modulating the immune system. For example, some immune cells release exosomes that carry antigens on their surface. These exosomes can then interact with other immune cells to help initiate an adaptive immune response against pathogens or tumors.
Factors Influencing Exosome Output
The production and release of exosomes is a dynamic process responsive to the cell’s condition and surrounding environment. For example, cells experiencing stress from a lack of oxygen (hypoxia), oxidative damage, or nutrient deprivation often increase their rate of exosome secretion. This response can be a way for stressed cells to communicate their state to neighboring cells to coordinate a collective response.
Different types of cells exhibit varying levels of exosome production, as specialized secretory cells may release more exosomes as part of their function. The composition of exosomes also differs depending on the cell of origin. For example, an exosome from a neuron will carry a different set of molecules than one from a skin cell, reflecting their distinct biological roles.
Pathological conditions, especially diseases like cancer, can alter exosome production. Tumor cells are known to release exosomes in much greater quantities than healthy cells. These cancer-derived exosomes can carry molecules that promote tumor growth, invasion, and the development of new blood vessels. By releasing these exosomes, cancer cells can manipulate their local environment and influence distant cells to create a setting for metastasis.