Cell Junctions Physiology Notes

Cell Junctions Definition And Classification

The cell junction is the connection between the neighboring cells or the contact between the cell and the extracellular matrix. It is also called a membrane junction.

Cell junctions are generally classified into three types:

1. Occluding junctions that prevent the intercellular exchange of substances
2. Communicating junctions which permit the intercellular exchange of substances
3. Anchoring junctions which provide strength to the cells by acting like mechanical attachments.

Read And Learn More: Medical Physiology Notes

Occluding Junctions

The junctions, which prevent the movement of ions and molecules from one cell to another cell are called the occluding junctions. Tight junctions belong to this category.

Tight Junction: 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. This type of junction is present in the apical margins of epithelial and endothelial cells in the intestinal mucosa, wall of the renal tubule, capillary wall, and choroid plexus.

Structure of Tight Junction: The tight junction is made up of a ridge. The ridge has two halves. One-half of the ridge is from one cell and another half is from the other cell. 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.

• The proteins involved in the formation of tight junctions are classified into two types:
  • Tight junction membrane proteins or integral membrane proteins, such as occludin, claudin, and junctional adhesion molecules (JAMs) Scaffold (framework or platform) proteins or peripheral membrane proteins or cytoplasmic plaque proteins such as cingulin, symplekin, and ZO-1, 2, 3.
  • The tight junction membrane protein molecules are anchored in the strands of the ridge and attach with their counterparts of neighboring cells so that both cells are held together. The scaffold (platform) proteins are attached to 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: The tight junction forms a selective barrier for small molecules and a total barrier for large molecules.

• In the epithelial and endothelial cells, the tight junction is the most apical intercellular junction which functions as a selective (semipermeable) diffusion barrier between the neighboring cells. This function is called a barrier or gate function. The 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. In some epithelial cells, some substances pass through the tight junction (by diffusion or active transport). In other cells, no substance passes through the tight junction.

3. Fencing function: The tight junction prevents the lateral movement of proteins (integral membrane proteins) and lipids in the cell membrane and thus acts as a fence. The fencing function maintains the different compositions of proteins and lipids between the apical and basolateral plasma membrane domains. Because of this function, the tight junction is some- times referred as an impermeable junction.

4. Maintenance of cell polarity: The 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: Tight junction in the brain capillaries forms the blood-brain barrier which prevents the entrance of many substances from capillary blood into brain tissues. Only lipid-soluble substances like drugs and steroid hormones can pass through the blood-brain barrier.

Tight Junction Applied Physiology:

• Diseases caused by the mutation of genes encoding proteins of the tight junction are:
  • Hereditary deafness
  • Ichthyosis (scaly skin)
  • Sclerosing cholangitis (inflammation of the bile duct causing obstruction)
  • Hereditary hypomagnesemia (low level of magnesium in the blood)
  • Synovial sarcoma (soft tissue cancer).
  • The functions of tight junctions are affected by some bacteria and viruses also.

Communicating Junctions

The junctions, which permit the movement of ions and molecules from one cell to another cell, are called communicating junctions. Gap junctions and chemical synapses are the communicating junctions.

Gap Junction:

The gap junction is the intercellular junction that allows the passage of ions and smaller molecules between the cells. It is also called nexus. It is present in the heart, basal part of epithelial cells of the intestinal mucosa, etc.

Structure of Gap Junction:

• The 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. The 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 ECF.
• 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. The 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 of less than 1,000
2. It helps in the exchange of chemical messengers between the cells
3. It helps in the rapid propagation of action potential from one cell to another cell.

Regulation Of The Diameter Of Channels In Gap Junction: In gap junctions, the diameter of each channel is regulated by the intracellular calcium ions. When the concentration of intracellular calcium ions increases, the protein subunits of connexin surrounding the channel come close to each other by sliding. Thus, the diameter of the channel decreases. The diameter of the channel is also regulated by pH, electrical potential, hormones or neurotransmitters.

Gap Junction Applied Physiology:

• Mutation in the genes encoding the connexins causes diseases such as:
  • Deafness
  • Keratoderma (thickening of the skin on palms and soles) FOCAL ADHESION
  • Cataract (opacity of lens in the eye)
  • Peripheral neuropathy (damage to the nerves of the peripheral nervous system)
  • Charcot-Marie-Tooth disease (a form of neuropathy)
  • Heterotaxia (abnormal arrangement of organs or parts of the body in relation to left-right symmetry).

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 the chemical transmitter for details).

Anchoring Junctions

• Anchoring junctions are the junctions, which provide firm structural attachment between two cells or between a cell and the extracellular matrix. Anchoring junctions are responsible for the structural integrity of the tissues and are present in the tissues like heart muscle and epidermis of the skin which are subjected to severe mechanical stress.
• The firm attachment between two cells or between a cell and the extracellular matrix is provided by either actin filaments or intermediate filaments.

Depending upon this, anchoring junctions are classified into four types:

1. Actin filament attachment
   1. Adherens junction (cell to cell)
   2. Focal adhesion (cell to matrix)
2. Intermediate filament attachment
   1. Desmosome (cell to cell)
   2. Hemidesmosome (cell to matrix)

Adherens Junction:

• 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. In adherence 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. Adherens junction is present in the intercalated discs between the branches of cardiac muscles. During the contractions and relaxation of the heart, the cardiac muscle fibers are held together tightly by means of this junction. The adherens junction present in the epidermis helps the skin to withstand mechanical stress.
• Focal adhesion is the cell-to-matrix junction, which connects the actin filaments of the cell to the extracellular matrix. In the epithelia of various organs, this junction connects the cells with their basal lamina. The trans-membrane proteins, which hold the cell membrane and the matrix, are called integrins.

Desmosome:

• It is a cell-to-cell junction, where the intermediate filaments connect two adjacent cells. Desmosome is also called macula adherens. The membranes of two adjacent cells, which oppose each other, are thickened and become spot-like patches. The intermediate filaments are attached to the thickened patches.
• Some of these filaments are parallel to the membrane and others are arranged in radiating fashion. Desmosomes function like tight junctions. The transmembrane proteins involved in desmosomes are mainly cadherins.

Hemidesmosome: Hemidesmosome is a cell-to-matrix junction, which connects the intermediate filaments of the cell to the extracellular matrix. This type of cell junction is like half desmosome and the thickening of the membrane of only one cell occurs. So, this is known as hemidesmosome or half desmosome. Mostly, the hemidesmosome connects the cells with their basal lamina. The proteins involved in this are integrins.

Applied Physiology:

• Dysfunction of adherens junction and focal junction in CAMS are classified into four types: colon due to mutation of proteins results in colon cancer. It also leads to tumor metastasis (the spread of cancer cells from a primary tumor to other parts of the body).
• Dysfunction of desmosome causes bullous pemphigoid (an autoimmune disease with tense blistering eruptions of the skin). Patients with this disease develop antibodies against cadherins.
  Dysfunction of hemidesmosomes also causes bullous pemphigoid. The patients develop antibodies against integrins.

Cell Adhesion Molecules

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). CAMs form the important structures of intercellular connections and are responsible for the structural organization of tissues.

Types Of Cell Adhesion Molecules:

• CAMs are classified into four types:

1. 1. Cadherins form the molecular limbs between neighboring cells. These CAMS form adherence junctions and desmosomes
   2. Integrins that form the focal adhesion and hemidesmosome
   3. IgG superfamily which forms the cell adhesion molecules in the nervous system
   4. Selectins which act as receptors for carbohydrates (ligands or mucin) and are found in leukocytes, platelets, and endothelial cells.