Introduction to Cell junctions .
Cell junction is the connection between the neighboring cells or the contact between the cell and extracellular matrix. It is also called membrane junction.
Classification of Cell junctions .
Cell junctions are classified into three types:
1. Occluding junctions .
2. Communicating junctions .
3. Anchoring junctions.
1. Occluding junctions .
Cell junctions which prevent intercellular exchange of substances are called occluding junctions, i.e. these junctions prevent the movement of ions and molecules from one cell to another cell. Tight junctions belong to this category.
Tight junction .
[1]. Tight junction is the intercellular occluding junction that prevents the passage of large molecules. It is also called zonula occludens. It is the region where the cell membranes of the adjacent cells fuse together firmly.
[2]. This type of junction is present in the apical margins of epithelial and endothelial cells in intestinal mucosa, wall of renal tubule, capillary wall and choroid plexus.
Structure of Tight Junction .
[1]. Tight junction is made up of a ridge which has two halves. One half of the ridge is from one cell and another half is from the other cell.
[2]. Both halves of the ridge fuse with each other very tightly and occupy the space between the two cells . Each half of the ridge consists of tight junction strands.
Proteins of tight junction .
Proteins involved in the formation of tight junctions are classified into two types:
[1] . Tight junction membrane proteins or integral membrane proteins, such as occludin, claudin and junctional adhesion molecules (JAMs) .
[2] . Scaffold (framework or platform) proteins or peripheral membrane proteins or cytoplasmic plaque proteins such as cingulin, symplekin and ZO1, 2, 3.
[3]. Tight junction membrane protein molecules are anchored in the strands of the ridge and attach with their counterparts of neighboring cell, so that both the cells are held together.
[4]. The scaffold (platform) proteins are attached with the tight junction membrane proteins and strengthen the anchoring in the ridges.
Functions of Tight Junction .
1. Strength and stability .
The tight junction holds the neighboring cells of the tissues firmly and thus provides strength and stability to the tissues.
2. Selective permeability (gate function) .
[2a]. The tight junction forms a selective barrier for small molecules and a total barrier for large molecules. In the epithelial and endothelial cells, tight junction is the most apical intercellular junction, which functions as selective (semipermeable) diffusion barriers between the neighboring cells. This function is called barrier or gate function.
[2b]. Barrier function of tight junction regulates the interchange of ions, water and varieties of macromolecules between the cells. The magnitude of this function varies in different tissues.
[2c]. In some epithelial cells, few substances pass through the tight junction (by diffusion or active transport). In other cells, no substance passes through the tight junction.
3. Fencing function .
[3a]. Tight junction prevents the lateral movement of proteins (integral membrane proteins) and lipids in cell membrane and thus acts as a fence.
[3b].The fencing function maintains the different composition of proteins and lipids between the apical and basolateral plasma membrane domains. Because of this function, the tight junction is sometimes referred as impermeable junction.
4. Maintenance of cell polarity .
Fencing function of the tight junction maintains the cell polarity by keeping the proteins in the apical region of the cell membrane.
5. Blood-brain barrier .
[5a]. Tight junction in the brain capillaries forms the blood brain barrier, which prevents the entrance of many substances from capillary blood into brain tissues.
[5b]. Only lipid soluble substances like drugs and steroid hormones can pass through the blood brain barrier.
2. Communicating junctions .
Cell junctions which permit the intercellular exchange of substances are called communicating junctions, i.e. these junctions permit the movement of ions and molecules from one cell to another cell. Gap junction and chemical synapse are the communicating junctions.
Gap junction .
Gap junction is the intercellular junction that allows passage of ions and smaller molecules between the cells. It is also called nexus. It is present in heart, basal part of epithelial cells of intestinal mucosa, etc.
Structure of Gap Junction .
[1]. Membranes of the two adjacent cells lie very close to each other and the intercellular space is reduced from the usual size of 2.5 to 3 nm.
[2]. Cytoplasm of the two cells is connected by the channels formed by the membranes of both cells. So, the molecules move from one cell to another cell directly through these channels, without having contact with extracellular fluid (ECF).
[3]. Each channel consists of two halves. Each half belongs to one of the two adjacent cells. Each half of the channel is surrounded by 6 subunits of proteins which are called connexins or connexons .
Functions of Gap Junction .
1. Diameter of the channel in the gap junction is about 1.5 to 3 nm. So, the channel permits the passage of glucose, amino acids, ions and other substances, which have a molecular weight less than 1,000
2. It helps in the exchange of chemical messengers between the cells
3. It helps in rapid propagation of action potential from one cell to another cell.
Regulation of the Diameter of Channels in Gap Junction .
[1]. In the gap junctions, the diameter of each channel is regulated by the intracellular calcium ions.
[2]. When the concentration of intracellular calcium ion increases, the protein subunits of connexin surrounding the channel come close to each other by sliding. Thus, the diameter of the channel decreases.
[3]. The diameter of the channel is also regulated by pH, electrical potential, hormones or neurotransmitter.
Chemical synapse .
Chemical synapse is the junction between a nerve fiber and a muscle fiber or between two nerve fibers, through which the signals are transmitted by the release of chemical transmitter .
Anchoring junctions .
[1]. Anchoring junctions are the junctions, which provide strength to the cells by acting like mechanical attachments, i.e. these junctions provide firm structural attachment between two cells or between a cell and the extracellular matrix .
[2]. Anchoring junctions are responsible for the structural integrity of the tissues and are present in the tissues like heart muscle and epidermis of skin, which are subjected to severe mechanical stress.
[3]. The firm attachment between two cells or between a cell and the extracellular matrix is provided by either actin filaments or the intermediate filaments.
[4]. Depending upon this, anchoring junctions are classified into 4 types:
1. Actin filament attachment .
i. Adherens junction (cell to cell)
ii. Focal adhesion (cell to matrix)
2. Intermediate filament attachment .
i. Desmosome (cell to cell)
ii. Hemidesmosome (cell to matrix)
Adherens junction .
[1]. Adherens junction is the cell to cell junction, which connects the actin filaments of one cell to those of another cell. In some places like epithelial linings, this junction forms a continuous adhesion (zonula adherens) just below the tight junctions.
[2]. In adherens junction, the membranes of the adjacent cells are held together by some transmembrane proteins called cadherins. Adherens junction provides strong mechanical attachments of the adjacent cells.
[3]. Adherens junction is present in the intercalated disks between the branches of cardiac muscles . During the contractions and relaxation of heart, the cardiac muscle fibers are held together tightly by means of this junction.
[4]. The adherens junction present in epidermis helps the skin to withstand the mechanical stress.
Focal adhesion .
[1]. Focal adhesion is the cell to matrix junctions, which connects the actin filaments of the cell to the extracellular matrix. In epithelia of various organs, this junction connects the cells with their basal lamina.
[2]. The transmembrane proteins, which hold the cell membrane and the matrix are called integrins.
Desmosome .
[1]. Desmosome is a cell to cell junction, where the intermediate filaments connect two adjacent cells. Desmosome is also called macula adherens.
[2]. The membranes of two adjacent cells, which oppose each other, are thickened and become spot like patches. Intermediate filaments are attached with the thickened patches.
[3]. Some of these filaments are parallel to the membrane and others are arranged in radiating fashion. Desmosomes function like tight junctions.
[4]. The transmembrane proteins involved in desmosome are mainly cadherins.
Hemidesmosome .
[1]. Hemidesmosome is a cell to matrix junction, which connects the intermediate filaments of the cell to the extracellular matrix.
[2]. This type of cell junction is like half desmosome and the thickening of membrane of only one cell occurs. So, this is known as hemidesmosome or half desmosome.
[3]. Mostly, the hemidesmosome connects the cells with their basal lamina. The proteins involved in this are integrins .
Cell adhesion molecules (CAMs) .
[1]. Cell adhesion molecules (CAMs) or cell adhesion proteins are the protein molecules, which are responsible for the attachment of cells to their neighbors or to basal lamina (or basal membrane).
[2]. CAMs form the important structures of intercellular connections and are responsible for structural organization of tissues.
Types of Cell Adhesion Molecules .
Cell adhesion molecules are classified into four types:
1. Cadherins, which form the molecular limbs between neighboring cells. These CAMs form adherens junction and desmosome
2. Integrins, which form the focal adhesion and hemidesmosome
3. IgG super family, which form the cell adhesion molecules in nervous system
4. Selectins, which act as receptors for carbohydrates (ligand or mucin) and are found in platelets and endothelial cells.




