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Cell Junctions Physiology

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Different cell junctions 

DEFINITION

Cell junction is the connection between neighboring cells or the contact between the cell and extracellular matrix. It is also called membrane junction. Connection between two cells is called intercellular junction. Tight junction, gap junction, adherence junc- tion and desmosome are intercellular junctions. Contact between the cell and extracellular matrix are focal adherence and hemidesmosome.

CLASSIFICATION 

Cell junctions are classified into three types: 

1. Occluding junctions.

2. Communicating junctions. 

3. Anchoring junctions.

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

 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 mem- branes of the adjacent cells fuse together firmly. This type of junction is present in the apical margins of epi- thelial and endothelial cells in intestinal mucosa, wall of renal tubule, capillary wall and choroid plexus.

Structure of Tight Junction 

Tight junction is made up of a ridge which has two halves. One half of the ridge is from one cell and an- other 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. 

Proteins of Tight Junction 

1. Tight junction membrane proteins or integral mem- brane proteins, such as occludin, claudin and junc- tional adhesion molecules (JAMS).

 2. Scaffold (framework or platform) proteins or peri- pheral membrane proteins or cytoplasmic plaque proteins such as cingulin, symplekin and ZO-1, 2,3. 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. 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

 Tight junction holds the neighboring cells of the tissues firmly and thus provides strength and stability to the tissues.

2. Selective permeability (gate function) 

Tight junction forms a selective barrier for small mole- cules 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. Barrier function of tight junction regulates the interchange of ions, water and varieties of macromol- ecules between the cells. The magnitude of this function varies in different tissues. 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 

Tight junction prevents the lateral movement of proteins (integral membrane proteins) and lipids in cell membrane and thus acts as a fence. 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

 Tight junction in the brain capillaries forms the blood- brain barrier (BBB), 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.

 APPLIED PHYSIOLOGY

 Diseases caused by mutation of genes encoding proteins of tight junction are listed below:

(Tight junction abnormally)

 Cause 

1. Mutation of encoding proteins in the genes of tight junction

2. Bacterial and viral infections

 Consequences

1. Hereditary deafness 

2. Ichthyosis (scaly skin) 

3. Sclerosing cholangitis (inflammation of bile duct causing obstruction)

4. Hereditary hypomagnesemia (low level of magnesium in the blood) 

5. Synovial sarcoma (soft tissue cancer)

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 mol- ecules from one cell to another cell. Gap junction and chemical synapse are the communicating junctions.

GAP JUNCTION 

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Gap junction

Gap junction is the intercellular junction that allows pas- sage 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

 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, 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 hav- ing contact with extracellular fluid (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. 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

 In the gap junctions, diameter of each channel is reg- ulated by the intracellular calcium ions. 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 diametor of the channel decreases. The diameter of the channel is also regulated by pH, electrical potential, hormones or neurotransmitters.

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 chem- ical transmitters.

APPLIED PHYSIOLOGY 

Mutation in the genes encoding the connexins causes diseases, which are given below:

Cause 

Mutation of gap junction proteins, particularly connexins (Gap junction abnormally)

Consequences 

1. Deafness 

2. Keratoderma (thickening of skin on palms and soles) 

3. Cataract (opacity of lens in eye) 

4. Peripheral neuropathy (damage to the nerves of peripheral nervous system) 

5. Charcot-Marie-Tooth disease (a form of neuropathy) 

6. Heterotaxia (abnormal arrangement of organs or parts of the body in relation to left-right symmetry)

ANCHORING JUNCTIONS 

Anchoring junctions are the junctions that provide strength to the cells by acting like mechanical attach- ments, i.e. these junctions 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 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 the intermediate filaments. Depend- ing upon this, anchoring junctions are classified into four types: 

1. Actin filament attachment: 

i. Adherens junction (cell to cell). 

ii. Focal adhesion (cell to matrix).

2. Intermediate filament attachment: 

iii. Desmosome (cell to cell). 

iv. 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 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. Adherens junction is pre- sent 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. The ad- herens junction present in epidermis helps the skin to withstand the mechanical stress. 

FOCAL ADHESION 

Focal adhesion is the cell to matrix junction, which connects the actin filaments of the cell to the extracel- lular matrix. In 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 

Desmosome is a cell to cell junction, where intermedi- ate 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. Intermediate filaments are attached with 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 desmosome are mainly cadherins. 

HEMIDESMOSOME 

Hemidesmosome is a cell to matrix junction, which con- nects the intermediate filaments of the cell to the ex- tracellular matrix. 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. Mostly, the hemidesmosome connects the cells with their basal lamina.

CELL ADHESION MOLECULES 

DEFINITION 

Cell adhesion molecules (CAMS) or cell adhesion proteins are the protein molecules situated on the cell surface. 

FUNCTIONS OF CELL ADHESION MOLECULES 

1. CAMS are responsible for the binding of cells to their neighbors or to basal lamina (or basal mem- brane). 

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 

Cadherins form the molecular limbs between neighbor- ing cells. These CAMS form adherens junction and des- mosome. 

2. Integrins 

Integrins form the focal adhesion and hemidesmosome.

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Source K Sembulingam's Physiology

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