CD63 is a protein found on the surface and within various cells throughout the human body. It is a member of the tetraspanin family, known for proteins with four segments that span the cell membrane. CD63 plays a role in various cellular processes, contributing to cell function and communication.
Understanding CD63
CD63 is a tetraspanin protein, characterized by its four transmembrane domains that weave through the cell’s outer membrane. This unique structure allows it to interact with other proteins both inside and outside the cell. It is found in several cellular locations, including the cell surface, as well as internal compartments like endosomes and lysosomes. Endosomes are sorting stations within the cell, and lysosomes are involved in waste breakdown and recycling.
Within these cellular compartments, CD63 participates in various functions. It is involved in cell adhesion, the process by which cells attach to each other and to their surrounding environment. CD63 also plays a role in cell migration, which is the movement of cells, a process important for development, wound healing, and immune responses. It can also influence cell survival and the reorganization of the cell’s internal scaffolding, known as the actin cytoskeleton.
CD63 can function as a cell surface receptor for certain proteins, such as TIMP1, and can activate cellular signaling pathways, including those involving AKT and MAP kinases. These signaling events contribute to processes like cell spreading and the regulation of how certain receptors, such as KDR/VEGFR2 involved in blood vessel growth, are internalized by the cell. Its involvement in intracellular vesicular transport processes directs substances within the cell, like the movement of PMEL, a protein important for melanocyte development.
CD63 as an Exosome Marker
CD63 holds particular significance due to its strong association with exosomes. These are tiny, membrane-bound sacs released by nearly all cell types into their environment. These small vesicles, typically ranging from 30 to 200 nanometers in diameter, carry a specific collection of proteins, genetic material like RNA, and lipids from their parent cells. Exosomes serve as messengers, transferring this molecular cargo to nearby or distant cells, thereby facilitating intercellular communication.
Exosomes originate within cells from structures called multivesicular bodies (MVBs), a type of endosome. Inside MVBs, smaller vesicles, known as intraluminal vesicles (ILVs), form by budding inward from the MVB membrane. When these MVBs fuse with the cell’s outer membrane, they release the ILVs into the extracellular space, at which point they are recognized as exosomes. CD63 is highly enriched on the membranes of these ILVs and subsequently on the secreted exosomes, making it a commonly used marker for their identification.
CD63 is thought to play a part in sorting specific cargo into these vesicles. Its presence is also linked to the endosomal sorting complex required for transport (ESCRT) machinery, which helps guide protein incorporation into ILVs.
Moreover, CD63’s presence in tetraspanin-enriched microdomains (TEMs) on cell membranes is thought to facilitate the organization and budding of these vesicles. While CD63 is widely used as an exosome marker, some research indicates that it can also be found in other types of extracellular vesicles. However, its consistent accumulation within MVBs and its prevalence in small extracellular vesicles make it a reliable indicator for exosome characterization.
CD63 in Health and Disease
The presence and expression levels of CD63, particularly in exosomes, offer valuable insights into various health conditions and diseases, making it a biomarker. In cancer, CD63 has roles in diagnosis, prognosis, and monitoring. Elevated levels of CD63 in exosomes derived from tumor cells have been observed in several cancers, including melanoma, breast cancer, and stomach cancer.
The detection of high CD63 levels in plasma exosomes shows promise for early detection of melanoma. In lung adenocarcinoma, lower CD63 expression has been associated with a poorer prognosis, particularly in earlier stages. Conversely, CD63 can sometimes act as a tumor suppressor, with its overexpression inhibiting the migration of certain cancer cells, such as hepatocellular carcinoma cells. Further research is needed to fully understand its precise function in different cancer types.
Beyond cancer, CD63 is involved in immune responses and inflammatory conditions. It is expressed on mast cells and eosinophils, immune cells that play a role in allergic reactions and inflammation. Upon activation, CD63 on these cells can move to the cell surface, correlating with the release of inflammatory mediators like histamine. Studies have shown that a lack of CD63 can lead to a significant decrease in mast cell degranulation, the process of releasing these mediators, thereby reducing acute allergic reactions.
This involvement in mast cell activation and degranulation suggests that CD63 could be a target for managing allergic inflammation. Its expression on platelets also increases during inflammatory states, indicating its role in the body’s response to injury or infection. Changes in CD63 expression or its presence in circulating exosomes thus provide a window into the body’s physiological state and disease progression.