Cadherins are a family of proteins that function like a molecular glue, holding cells together to form tissues and organs throughout the body. Located on the surface of cells, these proteins mediate cell-to-cell adhesion. Without cadherins, the intricate structures of our bodies would not be able to maintain their integrity.
The Structure and Mechanism of Cadherins
Each cadherin protein is a single-pass transmembrane protein, extending through the cell membrane. It consists of three main parts: an extracellular domain, a transmembrane domain, and a cytoplasmic domain. The extracellular domain interacts with other cells, while the transmembrane domain anchors the protein within the cell’s outer membrane.
Cadherin function depends on calcium ions, which bind to the extracellular domain and provide rigidity, allowing the protein to maintain its shape and facilitate cell-to-cell connections. Cadherins engage in “homophilic binding,” where a cadherin molecule on one cell binds to an identical cadherin molecule on an adjacent cell.
The cytoplasmic domain connects to the cell’s internal scaffolding, the actin cytoskeleton, through adapter proteins called catenins. This linkage to the cytoskeleton provides anchorage and stability for cell-cell junctions, allowing mechanical forces to be transmitted across cells and contributing to tissue strength. Catenins, such as beta-catenin and p120-catenin, play a role in stabilizing the cadherin complex and regulating its activity.
Major Types and Locations
The cadherin family includes several subgroups, with “classical” cadherins being well-studied for their roles in cell adhesion. Different types of cadherins are expressed in specific tissues, acting as specialized adhesion molecules for various cell populations. This differential expression ensures the precise organization of cells into distinct tissues.
E-cadherin, or epithelial cadherin, is found in epithelial tissues, which form the linings of organs and the outer layer of the skin. It maintains cohesive sheets of cells that characterize these tissues. N-cadherin, or neural cadherin, is expressed in the central nervous system, including neurons, and also in cardiac muscle cells. This cadherin helps form stable connections within neural circuits and contributes to the structural integrity of the heart.
P-cadherin, or placental cadherin, is located in the placenta, an organ that develops during pregnancy, and also in the epidermis, the outermost layer of the skin. Each of these classical cadherins plays a specific role in maintaining the structure and organization of its respective tissues.
Role in Tissue Development and Maintenance
Cadherins play a role during embryonic development, guiding the precise organization of cells into distinct tissues and organs. They are involved in cell sorting, where cells expressing the same type of cadherin tend to aggregate, while cells with different cadherins or expression levels will segregate. For example, during neural tube formation, E-cadherin expression decreases in certain ectodermal cells, while N-cadherin expression increases, leading to their segregation and proper formation of neural tissues.
Beyond embryonic formation, cadherins continue to maintain the integrity and organization of tissues throughout adult life. They help regulate cell migration, cell differentiation, and the overall size of cell populations within tissues. This continuous adhesive function ensures that tissues remain intact and function correctly, ensuring stable tissue architecture. The presence and proper function of cadherins are important for both the formation and ongoing health of the body’s complex structures.
Cadherins in Disease
Dysfunction of cadherins can have consequences, particularly in the context of disease, with cancer being a prominent example. In many types of cancer, cells lose the ability to produce or properly utilize E-cadherin. This loss of the “cellular glue” disrupts cell-cell adhesion within the primary tumor, allowing cancer cells to detach from the main mass.
The detachment of cancer cells is a key step in metastasis, the process by which cancer spreads to other parts of the body. This often involves a process called epithelial-mesenchymal transition (EMT), where stationary epithelial cells, which normally express E-cadherin, transform into more mobile, mesenchymal-like cells. During EMT, E-cadherin expression is typically downregulated or lost, contributing to the invasive and migratory capabilities of cancer cells. The loss of E-cadherin’s adhesive function directly facilitates the ability of cancer cells to escape the primary tumor and colonize distant sites.