Cadherins are a family of proteins that play an important role in how cells interact with one another. They are responsible for mediating cell-to-cell adhesion, where cells physically connect. This function is fundamental for the organization and maintenance of tissues, ensuring that cells form stable structures. Without proper cell adhesion, the complex architecture of organs and systems would not be possible.
Defining Cadherins
Cadherins are a class of type-1 transmembrane proteins, meaning they span across the cell membrane with parts both inside and outside the cell. Their defining characteristic is their dependence on calcium ions (Ca²⁺) to function, which is where their name, “calcium-dependent adhesion,” originates. These proteins are synthesized as polypeptides, around 720–750 amino acids long, and undergo modifications to become functional.
Each cadherin molecule has a structure that enables its adhesive role. It features an extracellular domain, which is the part extending outside the cell and is responsible for binding to other cadherins. This extracellular domain contains five tandem repeats, each about 100 amino acids long, with binding sites for calcium ions. A transmembrane domain anchors the protein in the cell membrane, while a cytoplasmic domain extends into the cell’s interior, interacting with internal machinery. The presence of calcium ions makes the extracellular domain rigid, necessary for effective connection with cadherin molecules on an adjacent cell.
Mechanism of Cell Adhesion
Cadherins facilitate cell-to-cell binding through homophilic binding. This means that a cadherin molecule on one cell will bind to an identical cadherin molecule on a neighboring cell. This self-recognition allows cells to sort themselves and form distinct tissues. For instance, cells containing N-cadherin cluster with N-cadherin-expressing cells, aiding in tissue organization.
The extracellular domains of cadherins from opposing cells engage in a “trans” interaction, bridging the space between the cells to form strong junctions. The stability and strength of these junctions are further enhanced by the connection of the cadherin’s cytoplasmic domain to the cell’s internal scaffolding, known as the cytoskeleton. This connection is mediated by linker proteins called catenins, such as beta-catenin and alpha-catenin. Beta-catenin binds directly to the cadherin’s cytoplasmic tail, then interacts with alpha-catenin, which associates with actin filaments of the cytoskeleton. This linkage provides mechanical strength and stability to the cell junctions, contributing to tissue integrity of tissues.
Roles in Biological Processes
Cadherins are important in many biological processes beyond cell adhesion. In embryonic development, they shape tissues and organs. For example, cadherins contribute to the compaction of the early embryo, the formation of the neural tube during nervous system development, and the segregation of different tissue layers. Their regulated expression guides cells to their correct positions and allows complex tissue structures to form.
Cadherins also maintain the integrity of adult tissues, particularly in epithelial layers like those lining the intestines or kidney tubules. They contribute to tissue homeostasis and repair, ensuring that cells remain connected and organized. Beyond static adhesion, cadherins influence cellular behaviors like cell migration and differentiation. Changes in cadherin expression allow cells to alter their adhesive properties, enabling them to move and differentiate into specialized cell types.
Cadherins and Disease
Cadherin dysfunction can contribute to various health issues, notably cancer progression. Altered or lost function of cadherins, particularly E-cadherin, is frequently observed in epithelial cancers. This reduction in cell adhesion can allow cancer cells to detach from the primary tumor, contributing to tumor invasion and metastasis (the spread of cancer cells). E-cadherin is sometimes called a “suppressor of invasion” due to its role in maintaining cell connections that restrict cell movement.
While E-cadherin loss is commonly associated with increased invasiveness, some studies suggest that in later stages of cancer, E-cadherin might promote cell migration and survival, highlighting its complex role. Beyond cancer, defects in cadherin function have also been implicated in other conditions affecting tissue integrity, including cardiovascular and neurodegenerative disorders. These examples underscore cadherins’ importance in maintaining healthy tissue structure and function.