Cadherins are a family of proteins that play an important role in holding cells together, forming the complex structures of tissues and organs in multicellular organisms. They function as molecular anchors, helping cells adhere and maintain structural integrity. This adhesion is essential for the development and function of all animal life.
The Basics of Cadherins
Cadherins are transmembrane proteins, spanning the cell membrane, with parts extending both outside and inside. They act as “molecular glue,” facilitating connections between neighboring cells. A cadherin’s structure includes an extracellular domain for binding to other cadherin molecules, a transmembrane domain anchoring the protein within the cell membrane, and an intracellular domain connecting to the cell’s internal machinery. This internal connection allows cadherins to influence cellular processes beyond just adhesion.
The extracellular domain is composed of multiple repeating protein chains, with calcium ion binding sites. Calcium ions are necessary for these chains to become rigid, allowing connection with cadherin chains on an adjacent cell. The intracellular portion forms a complex within the cell, linking external adhesion to internal cellular architecture.
How Cadherins Connect Cells
Cadherins connect cells through homophilic binding, where cadherin molecules on one cell bind to identical cadherin molecules on an adjacent cell. This ensures cells of the same type adhere, contributing to organized tissue formation. Cadherin adhesion depends on calcium ions, which rigidify extracellular domains and promote interactions. Without sufficient calcium, cadherin structure and adhesive capabilities are compromised.
The intracellular domain of cadherins interacts with adapter proteins called catenins (alpha, beta, and gamma). Beta-catenin links the cadherin to alpha-catenin. Alpha-catenin then connects this complex to the cell’s actin cytoskeleton, a network of protein filaments providing structural support and enabling cell movement. This connection provides mechanical strength to cell-cell adhesions and helps regulate cell behavior, including cell shape and position.
Diverse Cadherin Types and Their Specific Roles
The cadherin family has over 100 members in humans, categorized into several subfamilies. Classical cadherins are well-understood and characterized by five extracellular cadherin repeats. Their expression patterns across different tissues are important for the organization and development of organs.
E-cadherin (epithelial cadherin) is found predominantly in epithelial cells, forming linings and coverings throughout the body. It forms strong, stable cell-cell junctions essential for maintaining the integrity and polarity of epithelial tissues. N-cadherin (neural cadherin) is expressed in neural cells, muscle cells, and fibroblasts. It participates in dynamic processes, such as cell migration, synapse formation, and heart development. P-cadherin (placental cadherin) is present in the placenta, epidermis, and hair follicles, playing roles in cell proliferation and differentiation. Other cadherin types exist, like VE-cadherin in endothelial cells, which line blood vessels, and protocadherins, involved in neuronal survival and self-avoidance in dendrites.
Cadherins and Human Health
Disruptions in cadherin function have implications for human health, particularly in the context of disease progression. An example is the role of E-cadherin in cancer; a reduction or loss of E-cadherin expression is a sign of epithelial-mesenchymal transition (EMT), a process where cancer cells lose their adhesive properties. This loss allows cancer cells to detach from the primary tumor and spread to other parts of the body through metastasis.
Cadherins are also important in embryonic development, where their function is necessary for the formation of various tissues and organs. Defects in cadherin activity can lead to developmental abnormalities, affecting processes like neural tube formation and tissue differentiation. Furthermore, mutations in cadherin genes have been linked to genetic disorders affecting tissue integrity, such as skin and heart conditions. Research suggests their involvement in inflammatory processes, with some cadherins, like Cadherin-11, implicated in regulating inflammation in conditions such as rheumatoid arthritis and lupus. Understanding cadherin behavior is relevant for addressing various human diseases.