Cadherins

Cadherins

Cadherins are a class of type-1 transmembrane proteins that are critically involved in cell-cell adhesion, ensuring that cells within tissues are bound together. They are dependent on calcium ions (Ca²⁺) to function, which is reflected in their name, derived from "calcium-dependent adhesion." Cadherins play a crucial role in maintaining the structure and function of tissues and are involved in various cellular processes, including morphogenesis, tissue homeostasis, and tumor suppression.

Structure

Cadherins are composed of three main domains:

1. Extracellular domain: This domain contains multiple cadherin repeats, typically five, which are responsible for homophilic binding (binding to the same type of cadherin on an adjacent cell). The binding is calcium-dependent, and the presence of calcium ions stabilizes the cadherin structure, allowing for adhesion.
2. Transmembrane domain: This hydrophobic region anchors the cadherin in the cell membrane.
3. Cytoplasmic domain: This domain interacts with the cytoskeleton of the cell through catenins, linking cadherins to actin filaments and playing a role in signal transduction.

Types of Cadherins

Cadherins are classified into several subtypes based on their structure and function:

• Classical cadherins: These include E-cadherin (epithelial), N-cadherin (neural), and P-cadherin (placental). They are primarily involved in cell-cell adhesion in epithelial and neural tissues.
• Desmosomal cadherins: These include desmogleins and desmocollins, which are components of desmosomes, specialized structures that provide strong adhesion between cells in tissues subject to mechanical stress, such as the skin and heart.
• Protocadherins: A large subfamily of cadherins that are primarily expressed in the nervous system and are thought to play a role in the establishment of specific neuronal connections.

Function

Cadherins are essential for the formation and maintenance of adherens junctions, which are crucial for the structural integrity of tissues. They mediate cell-cell adhesion by forming homophilic interactions with cadherins on adjacent cells, creating a continuous adhesive belt around cells.

In addition to their structural role, cadherins are involved in signaling pathways that regulate cell proliferation, differentiation, and migration. They are key players in epithelial-mesenchymal transition (EMT), a process where epithelial cells lose their polarity and adhesion properties to become mesenchymal stem cells, which is important in development and cancer metastasis.

Clinical Significance

Alterations in cadherin expression and function are associated with various diseases, including cancer. Loss of E-cadherin expression is a hallmark of EMT and is associated with increased invasiveness and metastasis in epithelial tumors. Mutations in cadherin genes can lead to hereditary disorders, such as hereditary diffuse gastric cancer, which is linked to mutations in the CDH1 gene encoding E-cadherin.

Research and Therapeutic Potential

Understanding the role of cadherins in cell adhesion and signaling has significant implications for developing therapeutic strategies for cancer and other diseases. Targeting cadherin-mediated pathways could provide new avenues for inhibiting tumor progression and metastasis.

See Also

• Cell adhesion molecule
• Catenin
• Adherens junction
• Desmosome

References

• Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. (2002). Molecular Biology of the Cell. Garland Science.
• Takeichi, M. (1991). Cadherin cell adhesion receptors as a morphogenetic regulator. Science, 251(5000), 1451-1455.