Many types of cell-cell adhesion have been reported (Fig. 11-1). Major types will also be discussed in the section on tissue architecture. Here, we describe cadherins - common molecules that connect cells together and play a range of important roles.
Fig. 11-1. Cell adhesion model
Cell adhesions are classified into the binding of a cell to another cell or to extracellular matrix material. Cadherins, the immunoglobulin superfamily and selectins participate cell-cell adhesion. Integrins are involved in the adhesion of a cell to extracellular matrix materia
Discovery of Cadherin and its Characteristics
It has long been known in embryology that if an embryo is cultured in a Ca2+free medium, germ cells dissociate from each other, and reagguregate with the addition of Ca2+ to the medium,. To investigate this phenomenon, the molecules that stick germ cells together in the presence of Ca2+ were studied, and cadherin was discovered as a protein located on the plasma membrane called cadherin was discovered.
Several types of tissue-specific cadherin exist. As examples, E-cadherins are found in epithelial tissues, and N-cadherins are found in nerve tissues. These cadherins are bound only between the same types (e.g., E-cadherin and E-cadherin), and the presence of Ca2+ is essential for the adhesion via Cadherins.
Cadherin - a transmembrane protein that penetrates the plasma membrane - adheres to a cell that has the same type of cadherin using the part protruding from the cell (the extracellular domain). Extracellular signals (such as signals that indicate adherence to the same type cell) are conveyed to the cell using the part inside cells of cadherin protein (the intracellular domain). The intracellular domain of cadherin is attached to proteins that transduce extracellular signals into the cell. The intracellular domain is also bound with actin filaments, allowing the regulation of cytoskeletal construction by extracellular signals (Fig. 11-2).
Fig. 11-2. Adhesion model of cadherin
Cadherins not only mediate cell-cell adhesion, but also influence gene expression and the establishment of cytoskeletal networks. The intracellular domain of cadherin is bound with catenins (signal transducer proteins) and actin filaments (cytoskeletal components).
Roles of Cadherins
Cadherins within one group bind only to themselves. This characteristic plays an important role in tissue construction (discussed later), enabling cells of the same type bind together. Some other unique roles of cadherins are discussed below.
One of these is cell sorting, a well-known phenomenon that occurs during the developmental process of animals (Fig. 11-3A). As an example, if two types of cell, which have different cadherins are mixed and cultured, those with the same cadherins stick together and form two separate groups. This characteristic of cadherins plays an important role in the developmental process phenomenon in which a single cell group is separated into several cell groups to form different tissues and organs.
Another phenomenon involving cadherins is contact inhibition (Fig. 11-3B). As an example, if the number of cultured cells increases up to the point where they start to come into contact with each other, the cells stop dividing. Similarly, if migrating cells come into contact with each other, they temporarily stop moving and change direction to avoid one another. This phenomenon involves some types of cell adhesion molecule located on the plasma membrane, including cadherins.
Fig. 11-3. Cell sorting and contact inhibition
A) A model of cell sorting. If two types of cell with different cadherins are mixed, cells with the same cadherins selectively adhere to each other, forming two separate cell groups.
B) A model of contact inhibition. If normal cells come into contact with each other during their locomotion, they recognize one another through the contact and stop moving. Then, these cells start to avoid each other.
Other Cell-Cell Adhesion
In addition to cadherins, cell-cell adhesion involves the immunoglobulin superfamily and selectins. The immunoglobulin superfamily is a group of proteins that share structural features with immunoglobulins, and include many cell adhesion transmembrane proteins. Selectins, on the other hand, are transmembrane proteins that selectively adhere to particular carbohydrate chains located on the plasma membrane surface of other cells, and three types are known. They are found in the vascular system of vertebrates.