CADHERINES: STRUCTURE, CHARACTERISTICS AND FUNCTIONS - BIOLOGY - 2025

The cadherins are transmembrane glycoproteins dependent calcium and responsible for maintaining the connection between cells that maintain the integrity of tissues in animals. There are more than 20 different types of cadherins, all with about 750 amino acids, and which are specific to different types of cells.

The cell bonds achieved by cadherins are stable over time. Therefore, these molecules play an important role in the development of the shape of the organism during embryonic development (morphogenesis), as well as in the maintenance of the structure of tissues both in the embryonic stage and in adult life.

Molecular representation of the 1suh protein, E-cadherin (epithelial). Taken and edited from: Jawahar Swaminathan and MSD staff at the European Bioinformatics Institute.

The malfunction of cadherins is associated with the development of different types of cancer. Deficiency of cell adhesion through cadherins is one of the causes of increased motility of tumor cells.

Cell adhesion molecules

In multicellular organisms, cells must unite to participate in a great diversity of biological processes that allow maintaining their integrity, thus differentiating themselves from colonial unicellular organisms. These processes include, among others, hemostasis, immune response, morphogenesis, and differentiation.

These molecules differ in their structure, as well as in their function, into four groups: integrins, selectins, immunoglobulins, and cadherins.

History

The history of cadherins is very short, since they have been known for very little. Thus, the first cadherin was discovered in cells from mouse tissues in 1977. Scientists called this molecule uvomorulin.

In the 1980s, many other cadherin molecules were discovered in tissues from various species. These cadherins were found in calcium-dependent cell aggregation assays. All of them belonged to the same group of molecules called classical cadherins.

In recent years, and thanks to advances in molecular biology, scientists have managed to identify another important number of cadherins, some of which their specific function is unknown, and which could have functions other than cell adhesion.

Structure

Cadherins are glycoproteins, that is, molecules formed by the association of a protein and a carbohydrate. They are made up of between 700 (usually 750) and 900 amino acids, and have different functional domains, which allow them to interact in the first place with other cadherin molecules and with calcium ions.

Functional domains also allow cadherins to integrate into the plasma membrane, as well as to associate with the actin cytoskeleton. Most of the amino acid chain is located in the extracellular region and is normally differentiated into five domains, called EC (EC1-EC5).

Each of these domains has approximately 100 amino acids, with one or two calcium-binding sites. The transmembrane region is located between the outer and inner part of the cell and crosses the membrane only once.

On the other hand, the portion of cadherins found inside the cell is highly conservative and consists of 150 amino acids. This domain binds to the actin cytoskeleton by means of cytosolic proteins called catenins.

Types

There are more than 20 different types of cadherins, which are classified in different ways depending on the authors. Thus, for example, some authors recognize two groups or subfamilies, while others recognize six. According to the former, cadherins can be divided into:

Classic Cadherines or Type I

Also called traditional cadherins. Included in this group are cadherins that were named according to the tissue where they were first found, such as E-cadherin (epithelial), N-cadherin (neural), P-cadherin (placental), L-cadherin (liver) and R-cadherin (retina). However, these glycoproteins can be found in different tissues.

For example, N-cadherin, in addition to being present in neural tissue, can also be located in tissues of the testes, kidney, liver, and cardiac musculature.

Atypical or Type II cadherins

Also called non-traditional or non-classical. They include desmogleins and desmocholins, which form junctions at the level of intercellular desmosomes. There are also the protocadherins, characterized by lacking connections to the actin cytoskeleton.

All these cadherins are separated from other non-traditional ones, by some authors, into three independent groups. The rest of the atypical cadherins include T-cadherin, which lack transmembrane and cytoplasmic domains, and a variant of E-cadherin, which is found outside the cell and is called Evar-cadherin.

characteristics

They are calcium-dependent glycoproteins found almost exclusively in animal tissues. Most of them are single-pass transmembrane; in other words, they are present in the cell membrane, crossing it from side to side only once.

Cadherins participate mainly in the union between cells that present semilar phenotypic characteristics (homotypic or homophilic bonds). The cell bonds made by these molecules (cadherin-cadherin bonds) are about 200 times stronger than other protein-protein bonds.

In traditional cadherins the cytoplasmic domain is highly conservative. This means that its composition is similar in the different cadherins.

Features

The main function of cadherins is to allow permanent cell junctions over time, for which they play a fundamental role in processes such as embryonic development, morphogenesis, differentiation and structural maintenance of epithelial tissues in the skin and intestine, as well as the axon formation.

This function is regulated in part by the -COOH terminal present in the intracellular portion or domain of the glycoprotein. This terminal interacts with molecules called catenins, which in turn interact with elements of the cell's cytoskeleton.

Other functions of cadherins include selectivity (choosing which other cell to join) and cell signaling, establishing cell polarity, and regulation of apoptosis. The latter is a mechanism of cell death controlled internally by the same organism to regulate its development.

Cadherins and cancer

The malfunction of cadherins is implicated in the development of various types of cancer. This malfunction may be due to modifications in the expression of cadherins and catenins, as well as the activation of signals that prevent cells from joining.

By failing the cell binding of cadherins, this allows tumor cells to increase their motility and be released, then invade adjacent tissues through lymph nodes and blood vessels.

E-Cadherina Benigma from breast. Micrograph of atypical lobular hyperplasia. Taken and edited from: Nephron.

When these cells reach the target organs, they invade and proliferate, obtaining invasive and metastatic characters. Most of the studies that have related cadherins to carcinogenic growth processes have focused on E-cadherin.

This type of cadherin is involved in colon, stomach, breast, ovarian and lung cancer, among others. This, however, is not the only cadherin linked to cancer. N-cadherin, for example, plays a role in pleural mesotheliomas and rhabdomyosarcomas.

References

1. Cadherin. On Wikipedia. Recovered from en.wikipedia.org
2. D. Leckband & A. Prakasam (2006). Mechanism and dynamics of cadherin adhesion. Annual Review of Biomedical Engineering.
3. F. Nolletl, P. Kools P, & F. Van Roy (2000). Phylogenetic Analysis of the Cadherin Superfamily allows Identification of Six Major Subfamilies Beside Several Solitary Members. Journal of Molecular Biology.
4. J. Günther & E. Pedernera-Astegiano (2011). E-cadherin: a key element in neoplastic transformation. Journal of Evidence and Clinical Research.
5. L. Petruzzelli, M. Takami & D. Humes (1999). Structure and Function of Cell Adhesion Molecules. American Journal of Medicine.
6. U. Cavallaro & G. Christofori (2004). Cell adhesion and signaling by cadherins and Ig-CAM s in cancer. Nature Reviews Cancer.