Cluster of Differentiation 91 (CD91) is a large receptor protein found on the surface of many cell types. This protein acts as a versatile tool, embedded in the cell’s outer membrane, where it interacts with the surrounding environment. Its presence across different cells underscores its importance in fundamental biological activities.
The Structure and Location of CD91
CD91 is also known by another name, Low-density lipoprotein receptor-related protein 1, or LRP1. Scientists often use these names interchangeably in research and clinical contexts. The protein is encoded by the LRP1 gene.
Structurally, CD91 is a protein that gets processed into two distinct parts that remain linked. A large 515 kDa subunit stays entirely outside the cell, while a smaller 85 kDa subunit passes through the cell membrane, anchoring the entire structure. This two-part assembly can be imagined as an antenna on the cell’s surface.
The large external component contains multiple specific regions, or ligand-binding domains, that recognize and grab onto a wide variety of molecules. The smaller component not only holds the antenna in place but also extends into the cell’s interior, allowing it to transmit information inward.
CD91 is not found uniformly throughout the body; its expression is particularly high in certain cell types. Liver cells, known as hepatocytes, have a high concentration of this receptor, where it contributes to metabolic processes. It is also abundant on neurons in the brain and on smooth muscle cells that line the walls of blood vessels. Macrophages, a type of immune cell responsible for cleaning up cellular debris, also express high levels of CD91.
Cellular Cleanup and Cargo Transport
One of the most well-understood functions of CD91 is its role in endocytosis, a process where cells internalize substances from their surroundings. CD91 acts like a cellular recycling center, identifying and capturing specific molecules, or “cargo,” for removal. It is capable of binding to more than 30 different ligands, which include old, damaged, or excess proteins that could otherwise cause problems if left to accumulate.
The process begins when a target molecule, such as a complex of a protease with its inhibitor, binds to one of the external domains of CD91. This binding event causes the portion of the cell membrane containing the receptor to fold inward, creating a small bubble-like structure called a vesicle. This vesicle then pinches off from the surface and travels into the cell’s interior, carrying the captured cargo with it.
Once inside the cell, the vesicle delivers its contents to lysosomes, which are specialized compartments filled with enzymes that break down waste materials. The cargo is degraded into its basic components, which can then be reused by the cell. After releasing its cargo, the CD91 receptor is typically recycled back to the cell surface, ready to capture more molecules.
Cell Signaling and Communication
Beyond its duties in cargo transport, CD91 is a dynamic participant in cell signaling, acting as a communications hub that translates external cues into internal actions. When specific molecules bind to the receptor, it doesn’t just mark them for disposal; it can also initiate a cascade of signals within the cell. The binding event can influence a cell’s decisions regarding growth, movement, and survival.
The signaling process is mediated by the intracellular part of the CD91 protein. After a ligand binds to the external subunit, the internal tail can interact with a variety of cytoplasmic adaptor proteins. These interactions can activate kinase-dependent signaling pathways, which are chains of proteins that relay messages from the cell surface to the nucleus. This can lead to changes in gene expression, directing the cell to perform specific functions.
For example, CD91 can modulate the activity of other receptors on the cell surface, such as the platelet-derived growth factor (PDGF) receptor, influencing how cells respond to growth factors in their environment. This signaling capacity allows CD91 to play a part in complex biological processes, including the regulation of blood vessel integrity and the migration of cells during development or wound healing.
The Role of CD91 in Human Disease
Dysfunction of CD91 is implicated in several human diseases, and its role is particularly well-studied in Alzheimer’s disease. One of the hallmarks of Alzheimer’s is the accumulation of amyloid-beta peptides in the brain, which form toxic plaques. CD91 is one of the main receptors responsible for clearing amyloid-beta from the brain tissue. Studies have shown that the expression of CD91 decreases with age and is lower in the brains of Alzheimer’s patients, suggesting a reduction in this clearance function could contribute to disease progression.
In the cardiovascular system, CD91 is involved in the development of atherosclerosis, the hardening of arteries due to the buildup of plaques. The receptor helps liver cells remove cholesterol-rich lipoproteins from the blood. In the walls of blood vessels, CD91 in smooth muscle cells helps manage the response to vessel injury. Dysregulation of these functions can contribute to the lipid accumulation and inflammation that characterize atherosclerotic plaques.
The role of CD91 in cancer is complex and can be context-dependent. In some scenarios, it helps prevent cancer invasion by clearing enzymes called proteases that cancer cells use to break through tissues. However, in other contexts, signaling through CD91 has been shown to potentially promote tumor cell migration and survival.